Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000033.4(ABCD1):c.750G>C (p.Val250=)

CA238543

193032 (ClinVar)

Gene: ABCD1 (HGNC:215)

Condition: adrenoleukodystrophy (MONDO:0018544)

Inheritance Mode: X-linked inheritance

UUID: 596104d5-6f6e-4053-9e5e-70a0ae0b1f08

Approved on: 2026-04-16

Published on: 2026-04-16

HGVS expressions

NM_000033.4(ABCD1):c.750G>C (p.Val250=)

NM_000033.4:c.750G>C

NC_000023.11:g.153726016G>C

CM000685.2:g.153726016G>C

NC_000023.10:g.152991471G>C

CM000685.1:g.152991471G>C

NC_000023.9:g.152644665G>C

NG_009022.2:g.6149G>C

NG_023231.1:g.3731C>G

ENST00000218104.6:c.750G>C

ENST00000218104.5:c.750G>C

ENST00000370129.4:c.195G>C

NM_000033.3:c.750G>C

Likely Benign

PM2_Supporting BP4 BP7

Evidence Links 0

Expert Panel

Peroxisomal Disorders VCEP

Criteria Specification Information

Criteria Specification: ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Peroxisomal Disorders VCEP

The c.750G>C (NM_000033.4) variant in ABCD1 is a variant occurring in exon 1. This variant is absent from gnomAD v2.1.1 and v3.1.2. It is reported in gnomAD v4.1 at a frequency of 0.000001120 (1/892612 alleles) in the non-Finnish European population with no hemizygotes, which is below the threshold of 0.0000017 set by the Peroxisomal Disorders VCEP (PM2_Supporting). The results from SpliceAI in silico predictor give a score of 0, which suggests that the variant does not impact ABCD1 function (BP4, BP7). Although the Bayesian points system suggests that a total of -1 pt can yield a likely benign classification, it is conservative to assume a minimum score of -2 pts for likely benign classifications. In summary, the Peroxisomal Disorders VCEP classified the variant as likely benign using the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders Variant Curation Expert Panel: PM2_supporting, BP4, BP7 (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)

PM2_Supporting

This variant is absent from gnomAD v2.1.1 and v3.1.2. It is reported in gnomAD v4.1 at a frequency of 0.000001120 (1/892612 alleles) in the non-Finnish European population with no hemizygotes, which is below the threshold of 0.0000017 set by the Peroxisomal Disorders VCEP (PM2_Supporting).

BP4

Results from in the silico predictor SpliceAI suggest that the variant does not impact ABCD1 function (SpliceAI score: 0.0), which is below the threshold of 0.2 set by the ClinGen Peroxisomal Disorders VCEP.

BP7

The ABCD1 c.750G>C (p.Val250=) variant is a synonymous (silent) variant that is not predicted by SpliceAI to impact splicing (SpliceAI score: 0.0). Conservation is not considered in the BP7 code per the Walker et al guidance.

Curation History

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