ABCD1 p.Trp679Ter
c.2037G>A · rs1557055406 · VCV449353
ClinGen expert panel — Peroxisomal Disorders VCEP
Likely Pathogenic for adrenoleukodystrophy. Applied ACMG criteria (verbatim):
PVS1_Moderate PM2_Supporting PS4_Moderate PP4_Supporting
Curation rationale (ClinGen, verbatim)
The c.2037G>A (p.Trp679Ter)(NM_000033.4) variant in ABCD1 is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 10 that may cause loss of function of the protein, however it is predicted to escape nonsense mediated decay and remove <10% of the protein (PVS1_Moderate; PMID:30192042). At least one patient with this variant was positive for biochemical (C26 two tier measurement) and adrenal involvement, which is highly specific for adrenoleukodystrophy (PP4, PMID: 33920672). This variant has been reported in 2 heterozygote females with neurological impairments as measured by JOA and SSPROM scores meeting PP4_Supporting phenotype criteria (PS4_moderate; PMID: 24410807). This variant is absent from gnomAD v4.1 (PM2_Supporting). In summary, this variant meets the criteria to be classified as Likely Pathogenic for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal VCEP: PP4, PS4_moderate, PVS1_moderate, PM2_supporting. (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)
ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Consequence | nonsense (stop-gain) | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| NMD | escapes | premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.6, phastCons 1 |
| Overall | ||
| CADD | 41.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- ABCD1
- Protein
- p.Trp679Ter
- Coding
- c.2037G>A
- MANE Select
- NM_000033
- dbSNP
- rs1557055406
- Type
- single nucleotide variant
- Location
- chrX:153743534 (GRCh38)
- Structure
- AlphaFold pLDDT 81.58 · 14 PDB
- Residue 679
- the 'required for homodimerization' region; a UniProt-annotated variant site (in ald; amn-type); a β-strand; the abc transporter domain
Similar variants
- ABCD1 p.Trp679Arg Likely pathogenic ★ same residue
- ABCD1 p.Trp679Cys Uncertain significance ★ ⚠ same residue
- ABCD1 c.1635-2A>G Pathogenic ★★ same type
- ABCD1 c.1781-1G>C Pathogenic ★★ same type
- ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same type
- ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same type
- ABCD1 c.1866-1G>C Likely pathogenic ★★ same type
- ABCD1 c.1866-2A>T Likely pathogenic ★★ same type
Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →
Cite Sugi Variant
Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/abcd1-p-trp679ter (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown