{
  "data": {
    "@context": "https://erepo.genome.network/evrepo/api/context",
    "@id": "https://cgerepoapi/evrepo/api/summary/classification/443be01c-2b2e-4d13-aac0-25e3b3726250/doc/sepio/version/1.0.0",
    "assertionMethod": {
      "@id": "https://cspec.genome.network/cspec/SequenceVariantInterpretation/id/1537428517",
      "label": "ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0",
      "type": "VariantPathogenicityInterpretationGuideline",
      "version": "1.0.0"
    },
    "condition": {
      "@id": "https://api.monarchinitiative.org/api/bioentity/phenotype/MONDO:0018544",
      "id": "MONDO:0018544",
      "label": "adrenoleukodystrophy",
      "type": "GeneticCondition"
    },
    "evidenceLine": [
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1699",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/ei/1/1700",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                  "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/4/16",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1699/1701",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                          "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                          "type": "Agent"
                        },
                        "comments": "There are at least 3 patients meeting PP4_supporting criteria counting towards PS4, in addition to the patient considered for PP4 and the two brothers included in PP1. The ALD db reports a total of 7 patients (likely include the fetus described in Lan F et al. 2011 and the unpublished in addition to 2 of PS4,  1 of PP4 and 2 of PP1)",
                        "contributionDate": {
                          "date": "2026/4/16",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1699/1701",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/1/1700",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1699",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1780",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/ei/1/1781",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                  "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/4/16",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1780/1782",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                          "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                          "type": "Agent"
                        },
                        "comments": "c.649A>T p.Lys217* is listed as pathogenic, identified in a single ALD case (88). ",
                        "contributionDate": {
                          "date": "2026/4/16",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1780/1782",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/1/1781",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Not Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1780",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1696",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/ei/1/1697",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                  "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/4/16",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1696/1698",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                          "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                          "type": "Agent"
                        },
                        "comments": "Dvorakova et al, (2001) performed in vitro mutagenesis of plasmid of the wt human cDNA to obtain variants identified in the in the two brothers.  When transfected into X-ALD fibroblast (25% of WT beta-oxidation of VLCFA) K217E was not able to restore defective beta-oxidation, while the other variant (N13T) was able to restore to WT levels. ",
                        "contributionDate": {
                          "date": "2026/4/16",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1696/1698",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/1/1697",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1696",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1831",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/ei/1/1832",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                  "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/4/16",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1831/1833",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                          "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                          "type": "Agent"
                        },
                        "comments": "At least one patient with this variant displayed Addison's disease/adrenal insufficiency (C), with positive family history (similarly affected sibling)(D), and elevated VLCFAs (F), which is highly specific for adrenoleukodystrophy (PP4_Moderate), PMID: 11438993).",
                        "contributionDate": {
                          "date": "2026/4/16",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1831/1833",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/1/1832",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1831",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1678",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/ei/1/1679",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                  "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/4/16",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1678/1680",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                          "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                          "type": "Agent"
                        },
                        "comments": "Two brothers are described in Dvorakova et al., (2001)  with isolated adrenal insufficiency\n(Addison disease, ADO). All patients in this study had elevated concentration of VLCFA in serum or plasma.",
                        "contributionDate": {
                          "date": "2026/4/16",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1678/1680",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/1/1679",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1678",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1747",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/ei/1/1748",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                  "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/4/16",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1747/1749",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                          "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                          "type": "Agent"
                        },
                        "comments": "Revel score is confirmed to be 0.98, thus well above the specification threshold of 0.85 for pathogenicity.",
                        "contributionDate": {
                          "date": "2026/4/16",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1747/1749",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/1/1748",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1747",
        "type": "EvidenceLine"
      },
      {
        "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1636",
        "evidenceItem": [
          {
            "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/ei/1/1637",
            "contribution": [
              {
                "agent": {
                  "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                  "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                  "type": "Agent"
                },
                "contributionDate": {
                  "date": "2026/4/16",
                  "description": "Date on which this evidence was provided"
                },
                "contributionRole": {
                  "@id": "https://obofoundry.org/sepio/0000156",
                  "id": "SEPIO:0000516",
                  "label": "curator role",
                  "type": "ContributoryRole"
                },
                "type": "Contribution"
              }
            ],
            "evidenceLine": [
              {
                "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415099400/MONDO:0018544/105/el/0/1636/1638",
                "evidenceItem": [
                  {
                    "@id": "CG-PCER:curatorInference/CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "contribution": [
                      {
                        "agent": {
                          "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822",
                          "id": "CG-PCER-AGENT:CG_50049_EP177618055787822",
                          "type": "Agent"
                        },
                        "comments": "the variant is not present in gnomAD, v2.1, 3.1, 4.1",
                        "contributionDate": {
                          "date": "2026/4/16",
                          "description": "Date on which this evidence was provided"
                        },
                        "contributionRole": {
                          "@id": "https://obofoundry.org/sepio/0000156",
                          "id": "SEPIO:0000516",
                          "label": "curator role",
                          "type": "ContributoryRole"
                        },
                        "type": "Contribution"
                      }
                    ],
                    "id": "CA415099400/MONDO:0018544/105/ci/CA415099400/MONDO:0018544/105.002",
                    "type": "InfFromBkgrndSciKnow"
                  }
                ],
                "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1636/1638",
                "type": "EvidenceLine"
              }
            ],
            "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/1/1637",
            "statementOutcome": {
              "@id": "SEPIO:0000224",
              "label": "Met"
            },
            "type": "CriterionAssessment"
          }
        ],
        "evidenceStrength": {
          "@id": "https://obofoundry.org/sepio"
        },
        "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105/0/1636",
        "type": "EvidenceLine"
      }
    ],
    "id": "CG-PCER-VARINT:CA415099400/MONDO:0018544/105",
    "metadata": {
      "created": "2026-04-16T19:28:38.108Z",
      "note": "DISCLAIMER: While the data/content in this document is approved by ClinGen expert panel(s), the SEPIO schema presented here is an initial prototype and has not been reviewed nor finalized by the ClinGen Data Exchange Modeling Team. We expect it to differ significantly from the final schema.",
      "producedAtUTC": "Thu, 16 Apr 2026 19:28:37 -0000",
      "schemaLabel": "Evidence Repository.Beta-1 (Unofficial)",
      "version": "1.0.0"
    },
    "statementOutcome": {
      "@id": "https://loinc.org/LA26332-9",
      "id": "LN:LA26332-9",
      "label": "Likely Pathogenic"
    },
    "type": "VariantPathogenicityInterpretation",
    "uuid": "443be01c-2b2e-4d13-aac0-25e3b3726250",
    "variant": {
      "@id": "https://reg.genome.network/allele/CA415099400",
      "id": "CAR:CA415099400",
      "relatedContextualAllele": [
        {
          "alleleName": [
            {
              "name": "NM_000033.4:c.649A>G"
            }
          ],
          "preferred": true
        }
      ],
      "relatedIdentifier": [
        {
          "label": "NM_000033.4:c.649A>G"
        }
      ],
      "type": "CAR"
    }
  },
  "metadata": {
    "rendered": {
      "by": "https://erepo.genome.network/evrepo/api/summary/srvc",
      "when": "2026-10-26T21:17:00.735Z"
    }
  },
  "status": {
    "code": 200,
    "name": "OK"
  }
}