Is ABCD1 p.Val287Met (c.859G>A) pathogenic?

ABCD1 p.Val287Met (c.859G>A) is classified Likely benign in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-18). AlphaMissense: likely benign (0.2619); Very rare (popmax 0.00241%, amr); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Val287Met (c.859G>A)?

ABCD1 p.Val287Met (c.859G>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Val287Met (c.859G>A) in the general population?

ABCD1 p.Val287Met (c.859G>A) is very rare (popmax 0.00241%, amr) (gnomAD).

How is X-linked adrenoleukodystrophy inherited?

Typically X-linked dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about ABCD1 p.Val287Met (c.859G>A)?

AlphaMissense predicts likely benign (score 0.2619) — an in-silico prediction, not a clinical call.

ABCD1 p.Val287Met

c.859G>A · rs782206393 · VCV2183830

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2619 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00241%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
AlphaMissense	0.2619	likely benign
REVEL	0.701	pathogenic-leaning
SaProt	LLR -7.99	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	26.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00241% Admixed American · 1/41,533 alleles

Overall 8.51e-05% 1/1,175,541 alleles · very rare exomes 1/1,061,115 · genomes 0/114,426 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ABCD1
Protein: p.Val287Met
Coding: c.859G>A
MANE Select: NM_000033
dbSNP: rs782206393
Type: single nucleotide variant
Location: chrX:153726125 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 287: an α-helix; the abc transmembrane type-1 domain

Full ABCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

adrenoleukodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked adrenoleukodystrophy (Orphanet):

Inheritance: X-linked dominant
Onset: Adolescent, Adult, Childhood, Elderly
Prevalence: 1-9 / 1 000 000 (Israel)

Similar variants

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
ABCD1 c.901-1G>A Pathogenic ★★ same condition
ABCD1 c.901-5C>A 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-val287met (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown