Is ABCD1 p.Ala255Thr (c.763G>A) pathogenic?

ABCD1 p.Ala255Thr (c.763G>A) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-28). AlphaMissense: likely benign (0.3015); Very rare (popmax 0.00297%, eas).

How common is ABCD1 p.Ala255Thr (c.763G>A) in the general population?

ABCD1 p.Ala255Thr (c.763G>A) is very rare (popmax 0.00297%, eas) (gnomAD).

What do computational predictors say about ABCD1 p.Ala255Thr (c.763G>A)?

AlphaMissense predicts likely benign (score 0.3015) — an in-silico prediction, not a clinical call.

ABCD1 p.Ala255Thr

c.763G>A · rs782688967 · VCV2690808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3015 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00297%, eas)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3015	likely benign
REVEL	0.815	moderately pathogenic-leaning
SaProt	LLR -10.84	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	25.0	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 0.00297% East Asian · 1/33,634 alleles

Overall 9.18e-05% 1/1,089,167 alleles · very rare

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.Ala255Thr
Coding: c.763G>A
MANE Select: NM_000033
dbSNP: rs782688967
Type: single nucleotide variant
Location: chrX:153726029 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 255: the abc transmembrane type-1 domain

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

Similar variants

ABCD1 p.Ala255Pro Uncertain significance ★ ⚠ same residue
ABCD1 p.Ala255= Likely benign ★ same residue
ABCD1 p.Ala255fs Likely pathogenic ★ 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

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-ala255thr (accessed [today's date]).

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