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.601G>A (p.Val201Met)

CA10549981

585357 (ClinVar)

Gene: ABCD1 (HGNC:215)

Condition: adrenoleukodystrophy (MONDO:0018544)

Inheritance Mode: X-linked inheritance

UUID: 4408a239-4756-42b8-a60b-720440715873

Approved on: 2026-04-14

Published on: 2026-04-14

HGVS expressions

NM_000033.4(ABCD1):c.601G>A (p.Val201Met)

NM_000033.4:c.601G>A

NC_000023.11:g.153725867G>A

CM000685.2:g.153725867G>A

NC_000023.10:g.152991322G>A

CM000685.1:g.152991322G>A

NC_000023.9:g.152644516G>A

NG_009022.2:g.6000G>A

NG_023231.1:g.3880C>T

ENST00000218104.6:c.601G>A

ENST00000218104.5:c.601G>A

ENST00000370129.4:c.46G>A

NM_000033.3:c.601G>A

Benign

BA1 BP4

PP3

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.601G>A (NM_000033.4) variant in ABCD1 is a missense variant predicted to cause substitution of Valine by Methionine at amino acid 201 (p.Val201Met). The GrpMax filtering allele frequency is 0.001360, gnomAD v4.1, which is higher than the ClinGen Peroxisomal Disorders VCEP threshold of ≥0.00017 for BA1, and therefore meets this criterion (BA1). The computational predictor REVEL gives a score of 0.423, (threshold ≤0.5) and the splice site predictor SpliceAI indicated that the variant has no impact on splicing with a score of 0.00 for donor/acceptor and loss/gain (threshold ≤0.1), evidence that does not predict a damaging effect on ABCD1 function (BP4). In summary, this variant meets the criteria to be classified as Benign for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal VCEP: BA1, BP4. (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)

BA1

The GrpMax filtering allele frequency is 0.001360, gnomAD v4.1, which is higher than the ClinGen Peroxisomal Disorders VCEP threshold of ≥0.00017 for BA1, and therefore meets this criterion (BA1). p.Val201Met is present in 13 and 9 hemizygous individuals from gnomAD v2.1 and v3.1 respectively. However, of these individuals, only 3 and 1 hemizygous variant carriers are over 40y.

BP4

The computational predictor REVEL gives a score of 0.423, (threshold ≤0.5) and the splice site predictor SpliceAI indicated that the variant has no impact on splicing with a score of 0.00 for donor/acceptor and loss/gain (threshold ≤0.1), evidence that does not predict a damaging effect on ABCD1 function (BP4).

PP3

REVEL score of 0.423 is consistent with a non pathogenic or neutral variant effect since it is below the cut-off 0.85

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.