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.2043C>G (p.Phe681Leu)

CA10550392

669027 (ClinVar)

Gene: ABCD1 (HGNC:215)

Condition: adrenoleukodystrophy (MONDO:0018544)

Inheritance Mode: X-linked inheritance

UUID: 0c07af21-2a6a-4805-b8d8-17f1b45fc8e3

Approved on: 2026-04-15

Published on: 2026-04-15

HGVS expressions

NM_000033.4:c.2043C>G

NM_000033.4(ABCD1):c.2043C>G (p.Phe681Leu)

NC_000023.11:g.153743540C>G

CM000685.2:g.153743540C>G

NC_000023.10:g.153008994C>G

CM000685.1:g.153008994C>G

NC_000023.9:g.152662188C>G

NG_009022.2:g.23673C>G

ENST00000218104.6:c.2043C>G

ENST00000218104.5:c.2043C>G

NM_000033.3:c.2043C>G

Benign

BA1

BP4 PP3 PM1

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

Evidence Summary: The c.2043C>G (NM_000033.4) variant in ABCD1 is a variant occurring in exon 10. The GrpMax filtering allele frequency in gnomAD v4.1 is 0.0003710 (19/33487 alleles) in the East Asian population with 6 hemizygotes, which is higher than the ClinGen Peroxisomal Disorders threshold (≥0.017% (0.00017)) for BA1. In summary, this variant meets the criteria to be classified as benign for adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders Variant Curation Expert Panel: BA1 (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 in gnomAD v4.1 is 0.0003710 (19/33487 alleles) in the East Asian population with 6 hemizygotes, which is higher than the ClinGen Peroxisomal Disorders threshold (≥0.017% (0.00017)) for BA1. The filtering allele frequency (the lower threshold of the 95% CI of 27/13704 (5 hemizygotes, 1 homozygote) of the c.2043C>G variant in ABCD1 is 0.001970 for East Asian chromosomes by gnomAD v21.1, which is higher than the ClinGen Peroxisomal Disorders threshold (≥0.017% (0.00017)) for BA1, and therefore meets this criterion (BA1). Variant not present in gnomAD v31.2.

BP4

The computational predictor REVEL gives a score of 0.638, which is above the BP4 threshold of 0.5., but below the PP3 threshold of 0.85. The SpliceAI score for acceptor loss was 0.01, while donor loss, acceptor gain, and donor gain was 0.00, which is less than the ClinGen Peroxisomal Disorders threshold of ≤ 0.2 for BP4. The results from 2 in silico predictors, REVEL and SpliceAI, do not agree, providing no evidence that correlates with a damaging or benign impact on ABCD1 function.

PP3

The computational predictor REVEL gives a score of 0.638, which is above the BP4 threshold of 0.5., but below the PP3 threshold of 0.85. The SpliceAI score for acceptor loss was 0.01, while donor loss, acceptor gain, and donor gain was 0.00, which is less than the ClinGen Peroxisomal Disorders threshold of ≤ 0.2 for PP4. The results from 2 in silico predictors, REVEL and SpliceAI, do not agree, providing no evidence that correlates with a damaging or benign impact on ABCD1 function.

PM1

This variant does not reside within a region of ABCD1 that is defined as a mutational hotspot or critical functional domain by the ClinGen Peroxisomal Disorders.

Curation History

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