{ "data": { "@context": "https://erepo.genome.network/evrepo/api/context", "@id": "https://cgerepoapi/evrepo/api/summary/classification/472c630c-6fa4-40e0-9bd6-a3a5ba108e43/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/CA415101152/MONDO:0018544/105/el/0/1735", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/MONDO:0018544/105/ei/1/1736", "contribution": [ { "agent": { "@id": "https://erepo.genome.network/evrepo/api//agent/CG_50049_EP177618055787822", "id": "CG-PCER-AGENT:CG_50049_EP177618055787822", "type": "Agent" }, "contributionDate": { "date": "2026/4/17", "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/CA415101152/MONDO:0018544/105/el/0/1735/1737", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415101152/MONDO:0018544/105/ci/CA415101152/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": "This variant has been reported in 1 proband meeting phenotype criteria for ABCD1 deficiency (PMID: 7668254). This is the same proband counted in PP4, with additional information obtained through personal communication. Therefore, PS4_Supporting not met.", "contributionDate": { "date": "2026/4/17", "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": "CA415101152/MONDO:0018544/105/ci/CA415101152/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1735/1737", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/1/1736", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1735", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/MONDO:0018544/105/el/0/1696", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/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": "2026/4/17", "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/CA415101152/MONDO:0018544/105/el/0/1696/1698", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415101152/MONDO:0018544/105/ci/CA415101152/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": "In Takahashi et al., 2007 (PMID: 17542813) p.Ser342Pro His-ALDP was expressed at comparable levels to that of wild type His-ALDP by immunoblotting. Beta-oxidation activity was not restored by the transfection of each mutant cDNA. Subcellular localization of S342P exhibited a punctate staining pattern in the cells suggesting this mutant His ALDPs was correctly localized to peroxisomes. As G116R and S342P are located to TMDs, substitution of these amino acids seems to affect substrate binding or transport through ALDP. This variant was not studied in van de Stadt et al, 2021. In Jia Yutian 2022, transport activity and ATP hydrolysis of six mutants was investigated. All six mutants showed decreased transport toward three species of VLCFA-CoA but S342P, in contrast with the other five, did not show abrogated ATP hydrolysis. In Watkins PA 1995, fibroblast of patient 4 with S342P showed normal punctate ALDP immunofluorescence pattern. Protein is described as stable but not functioning. The S342P is described as possibly changing the hydrophobicity of the residue.\nThe strength level is supporting based on the beta-oxidation activity findings, and moderate level is not applied due to the expression levels comparable to WT and the normal localization to peroxisomes.", "contributionDate": { "date": "2026/4/17", "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": "CA415101152/MONDO:0018544/105/ci/CA415101152/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1696/1698", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/1/1697", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1696", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/MONDO:0018544/105/el/0/1831", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/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": "2026/4/17", "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/CA415101152/MONDO:0018544/105/el/0/1831/1833", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415101152/MONDO:0018544/105/ci/CA415101152/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 adrenomyeloneuropathy, elevated VLCFAs and positive family history, which is highly specific for ABCD1 deficiency (PP4_Moderate, Internal lab contribution).\n\n", "contributionDate": { "date": "2026/4/17", "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": "CA415101152/MONDO:0018544/105/ci/CA415101152/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1831/1833", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/1/1832", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1831", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/MONDO:0018544/105/el/0/1678", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/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": "2026/4/17", "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/CA415101152/MONDO:0018544/105/el/0/1678/1680", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415101152/MONDO:0018544/105/ci/CA415101152/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 has been reported to segregate with ABCD1 deficiency in 1 affected\nfamily member from 1 family (PP1; Internal lab contribution).", "contributionDate": { "date": "2026/4/17", "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": "CA415101152/MONDO:0018544/105/ci/CA415101152/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1678/1680", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/1/1679", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1678", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/MONDO:0018544/105/el/0/1747", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/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": "2026/4/17", "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/CA415101152/MONDO:0018544/105/el/0/1747/1749", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415101152/MONDO:0018544/105/ci/CA415101152/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": "p.Ser342Pro has a revel score of 0.853 which is above the specifications cut-off (0.85) supporting role of pathogenicity. ", "contributionDate": { "date": "2026/4/17", "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": "CA415101152/MONDO:0018544/105/ci/CA415101152/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1747/1749", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/1/1748", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1747", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/MONDO:0018544/105/el/0/1636", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/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": "2026/4/17", "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/CA415101152/MONDO:0018544/105/el/0/1636/1638", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415101152/MONDO:0018544/105/ci/CA415101152/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": "p.Ser342Pro is absent in gnomAD v2.1, 3.1 and 4", "contributionDate": { "date": "2026/4/17", "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": "CA415101152/MONDO:0018544/105/ci/CA415101152/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1636/1638", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/1/1637", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1636", "type": "EvidenceLine" }, { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/MONDO:0018544/105/el/0/1780", "evidenceItem": [ { "@id": "https://erepo.genome.network/evrepo/api/interpretation/CA415101152/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": "2026/4/17", "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/CA415101152/MONDO:0018544/105/el/0/1780/1782", "evidenceItem": [ { "@id": "CG-PCER:curatorInference/CA415101152/MONDO:0018544/105/ci/CA415101152/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 c.1025C>T(p.Ser342Leu) has been identified 4x in ALD newborn screening (ref. 191, 200, 274 in the ALD database) but yet to be associated with disease", "contributionDate": { "date": "2026/4/17", "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": "CA415101152/MONDO:0018544/105/ci/CA415101152/MONDO:0018544/105.002", "type": "InfFromBkgrndSciKnow" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1780/1782", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/1/1781", "statementOutcome": { "@id": "SEPIO:0000224", "label": "Not Met" }, "type": "CriterionAssessment" } ], "evidenceStrength": { "@id": "https://obofoundry.org/sepio" }, "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105/0/1780", "type": "EvidenceLine" } ], "id": "CG-PCER-VARINT:CA415101152/MONDO:0018544/105", "metadata": { "created": "2026-04-17T14:25:20.190Z", "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": "Fri, 17 Apr 2026 14:25:20 -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": "472c630c-6fa4-40e0-9bd6-a3a5ba108e43", "variant": { "@id": "https://reg.genome.network/allele/CA415101152", "id": "CAR:CA415101152", "relatedContextualAllele": [ { "alleleName": [ { "name": "NM_000033.4:c.1024T>C" } ], "preferred": true } ], "relatedIdentifier": [ { "label": "NM_000033.4:c.1024T>C" } ], "type": "CAR" } }, "metadata": { "rendered": { "by": "https://erepo.genome.network/evrepo/api/summary/srvc", "when": "2026-10-14T02:08:48.240Z" } }, "status": { "code": 200, "name": "OK" } }