Is ABCD1 p.Ala394Val (c.1181C>T) pathogenic?

ABCD1 p.Ala394Val (c.1181C>T) is classified Conflicting classifications of pathogenicity in ABCD1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-04-22). AlphaMissense: ambiguous (0.3498); Very rare (popmax 0.00447%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Ala394Val (c.1181C>T)?

ABCD1 p.Ala394Val (c.1181C>T) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Ala394Val (c.1181C>T) in the general population?

ABCD1 p.Ala394Val (c.1181C>T) is very rare (popmax 0.00447%, nfe) (gnomAD).

What do computational predictors say about ABCD1 p.Ala394Val (c.1181C>T)?

AlphaMissense predicts ambiguous (score 0.3498) — an in-silico prediction, not a clinical call.

ABCD1 p.Ala394Val

c.1181C>T · rs1324874967 · VCV566056

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.3498 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00447%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3498	ambiguous
REVEL	0.614	indeterminate
SaProt	LLR -9.90	tolerated
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	23.2	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 0.00447% European (non-Finnish) · 40/895,302 alleles

Filtering AF 0.00337% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00296%

Overall 0.00347% 42/1,210,439 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00447%	22,383
Admixed American	0.00218%	45,887
Remaining individualsnot grpmax-eligible	0.0021%	47,595

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.Ala394Val
Coding: c.1181C>T
dbSNP: rs1324874967
Type: single nucleotide variant
Location: chrX:153736211 (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-ala394val (accessed [today's date]).

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