ABCD1 p.Met1Val
c.1A>G · rs2091702389 · VCV851448
ClinGen expert panel — Peroxisomal Disorders VCEP
Likely Pathogenic for adrenoleukodystrophy. Applied ACMG criteria (verbatim):
PVS1_Moderate PM2_Supporting PS3_Supporting PS4 PP4
Curation rationale (ClinGen, verbatim)
The c.1A>G (p.Met1Val) variant in ABCD1 may cause a truncated or absent protein by altering the start codon of the coding sequence (PVS1_Moderate). At least one patient with this variant displayed a primary adrenal insufficiency and increased plasma VLCFAs, which is highly specific for X-linked adrenoleukodystrophy (PP4; PMID:22176151). This variant has been reported in six more male probands meeting with a primary adrenal insufficiency and increased VLCFA ratios (PS4; PMID:34946879). This variant is absent from gnomAD v2.1.1, v3.1.2 and v4.1.0 (PM2_Supporting). Immunoblotting in transformed clonal cell lines showed severely reduced expression indicating that this variant impacts protein function. Beta-oxidation assay in transformed clonal cell lines showed the variant activity to be about 19.6% of wild type activity indicating that this variant impacts protein function (PMID:27067449, PS3_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 Disorders VCEP: PVS1_Moderate, PS4, PP4, PM2_Supporting, PS3_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 | start-loss | predicted loss-of-function in a haploinsufficient gene (ClinGen) |
|---|---|---|
| REVEL | 0.591 | indeterminate |
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 11 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 20.9 | 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.Met1Val
- Coding
- c.1A>G
- MANE Select
- NM_000033
- dbSNP
- rs2091702389
- Type
- single nucleotide variant
- Location
- chrX:153725267 (GRCh38)
- Structure
- AlphaFold pLDDT 81.58 · 14 PDB
Disease context
adrenoleukodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor X-linked adrenoleukodystrophy (Orphanet):
- Inheritance
- X-linked dominant
- Onset
- Adolescent, Adult, Childhood, Elderly
- Prevalence
- 1-9 / 1 000 000 (Israel)
Similar variants
- ABCD1 p.Met1_Pro2delinsIleSer Pathogenic ★ same residue
- ABCD1 p.Met1fs Pathogenic ★ same residue
- ABCD1 c.1635-2A>G Pathogenic ★★ same condition
- ABCD1 c.1781-1G>C Pathogenic ★★ same condition
- ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same condition
- ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same condition
- ABCD1 c.1866-1G>C Likely pathogenic ★★ same condition
- ABCD1 c.1866-2A>T Likely pathogenic ★★ same condition
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-met1val (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown