Is ABCD1 p.Ala273Val (c.818C>T) pathogenic?

ABCD1 p.Ala273Val (c.818C>T) is classified Uncertain significance in ABCD1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-01-24). AlphaMissense: likely pathogenic (0.705); Very rare (popmax 0.0023%, amr); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Ala273Val (c.818C>T)?

ABCD1 p.Ala273Val (c.818C>T) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Ala273Val (c.818C>T) in the general population?

ABCD1 p.Ala273Val (c.818C>T) is very rare (popmax 0.0023%, 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.Ala273Val (c.818C>T)?

AlphaMissense predicts likely pathogenic (score 0.705) — an in-silico prediction, not a clinical call.

ABCD1 p.Ala273Val

c.818C>T · rs868992338 · VCV446782

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0023%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
AlphaMissense	0.705	likely pathogenic
REVEL	0.889	moderately pathogenic-leaning
SaProt	LLR -12.00	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.38	donor gain · deltas
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0023% Admixed American · 1/43,546 alleles

Overall 0.000186% 2/1,073,525 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0023%	43,546
European (non-Finnish)	0.000113%	882,870

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.Ala273Val
Coding: c.818C>T
MANE Select: NM_000033
dbSNP: rs868992338
Type: single nucleotide variant
Location: chrX:153726084 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 273: 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 p.Ala273Glu Uncertain significance ★★ ⚠ same residue
ABCD1 p.Ala273Ser Uncertain significance ★ ⚠ same residue
ABCD1 p.Ala273= Likely benign ★ 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

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-ala273val (accessed [today's date]).

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