Is ABCD1 p.Val467Met (c.1399G>A) pathogenic?

ABCD1 p.Val467Met (c.1399G>A) is classified Conflicting classifications of pathogenicity in ABCD1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-03-22). AlphaMissense: likely benign (0.2515); Ultra-rare (popmax 0.0282%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Val467Met (c.1399G>A)?

ABCD1 p.Val467Met (c.1399G>A) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Val467Met (c.1399G>A) in the general population?

ABCD1 p.Val467Met (c.1399G>A) is ultra-rare (popmax 0.0282%, amr) (gnomAD).

What do computational predictors say about ABCD1 p.Val467Met (c.1399G>A)?

AlphaMissense predicts likely benign (score 0.2515) — an in-silico prediction, not a clinical call.

ABCD1 p.Val467Met

c.1399G>A · rs192525493 · VCV1686420

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2515 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0282%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2515	likely benign
REVEL	0.758	pathogenic-leaning
SaProt	LLR -10.78	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	25.7	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 0.0282% Admixed American · 13/46,054 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0132%

Overall 0.0014% 17/1,210,886 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0282%	3,543
Remaining individualsnot grpmax-eligible	0.0021%	47,635
European (non-Finnish)	0.000335%	298,427

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.Val467Met
Coding: c.1399G>A
dbSNP: rs192525493
Type: single nucleotide variant
Location: chrX:153737162 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: adrenoleukodystrophy

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-val467met (accessed [today's date]).

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