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.54G>A (p.Thr18=)

CA10549902

444828 (ClinVar)

Gene: ABCD1 (HGNC:215)

Condition: adrenoleukodystrophy (MONDO:0018544)

Inheritance Mode: X-linked inheritance

UUID: f60baeb0-e0a6-4c3b-96aa-5a7d6929c12c

Approved on: 2026-04-15

Published on: 2026-04-15

HGVS expressions

NM_000033.4(ABCD1):c.54G>A (p.Thr18=)

NM_000033.4:c.54G>A

NC_000023.11:g.153725320G>A

CM000685.2:g.153725320G>A

NC_000023.10:g.152990775G>A

CM000685.1:g.152990775G>A

NC_000023.9:g.152643969G>A

NG_009022.2:g.5453G>A

NG_023231.1:g.4427C>T

ENST00000218104.6:c.54G>A

ENST00000218104.5:c.54G>A

NM_000033.3:c.54G>A

Likely Benign

BP7 BP4 BS1

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.54G>A variant (NM_000033.4) is a synonymous (silent) variant (p.Thr18=) that is not predicted by SpliceAI to impact splicing. The filtering allele frequency (the lower threshold of the 95% CI of 41/1036386) of the c.55G>T (p.Ala19Ser) variant in ABCD1 is 0.00002617 for non-Finnish European exomes by gnomAD v4.1, which is higher than the ClinGen Peroxisomal Disorders VCEP threshold (>=0.000017) for BS1, and therefore meets this criterion (BS1). 10 hemizygotes are noted in gnomAD v4.1 for this variant. The computational splicing predictor SpliceAI gives a score of 0 for donor and acceptor loss and gain, suggesting that the variant has no impact on splicing. The exonic variant in exon 1 is not located in the first or last three bases of the exon. (BP4, BP7). In summary, this variant meets the criteria to be classified as likely benign for X-linked ABCD1 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders VCEP: BS1, BP4, BP7. (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)

BP7

The computational splicing predictor SpliceAI gives a score of 0 for donor and acceptor loss and gain, suggesting that the variant has no impact on splicing. The exonic variant in exon 1 is not located in the first or last three bases of the exon. (BP7)

BP4

The computational splicing predictor SpliceAI gives a score of 0 for donor and acceptor loss and gain, suggesting that the variant has no impact on splicing (BP4)

BS1

The filtering allele frequency (the lower threshold of the 95% CI of 41/1036386) of the c.55G>T (p.Ala19Ser) variant in ABCD1 is 0.00002617 for non-Finnish European exomes by gnomAD v4.1, which is higher than the ClinGen Peroxisomal Disorders VCEP threshold (>=0.000017) for BS1, and therefore meets this criterion (BS1). 10 hemizygotes are noted in gnomAD v4.1 for this variant.

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.