Is ABCD1 p.Gln544Arg (c.1631A>G) pathogenic?

ABCD1 p.Gln544Arg (c.1631A>G) is classified Likely pathogenic in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-04). AlphaMissense: likely pathogenic (0.988); Absent from gnomAD v4.1; Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Gln544Arg (c.1631A>G)?

ABCD1 p.Gln544Arg (c.1631A>G) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Gln544Arg (c.1631A>G) in the general population?

ABCD1 p.Gln544Arg (c.1631A>G) is absent from gnomAD v4.1 (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.Gln544Arg (c.1631A>G)?

AlphaMissense predicts likely pathogenic (score 0.988) — an in-silico prediction, not a clinical call.

ABCD1 p.Gln544Arg

c.1631A>G · rs2091763089 · VCV837244

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.988 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adrenoleukodystrophy

ClinGen expert panel — Peroxisomal Disorders VCEP

Likely Pathogenic for adrenoleukodystrophy. Applied ACMG criteria (verbatim):

PM2_Supporting PS3_Supporting PS4 PP3 PP4

Curation rationale (ClinGen, verbatim)

The c.1631A>G (p.Gln544Arg) variant in ABCD1 is a missense variant predicted to cause substitution of glutamine by arginine at amino acid 544 (p.Gln544Arg). At least one patient with this variant displayed rapid progression of inflammatory white matter demyelination in childhood and abnormal very long chain fatty acid testing, which is highly specific for adrenoleukodystrophy (PP4, PMID:10190819). This variant has been reported in 5 additional probands meeting PP4 phenotype criteria (PS4; PMIDs 21068741, 32632637, 10190819, 20661612). This variant is absent from gnomAD v2.1.1, v3.1.2 and v4.1.0 (PM2_Supporting). Beta-oxidation assay in X-ALD fibroblasts (163T) showed that the beta-oxidation activity of the variant protein is approximately 1.6% of wild type ABCD1, indicating that this variant has impact protein function (PMID:17542813)(PS3_Supporting). The computational predictor REVEL gives a score of 0.958, which is above the threshold of 0.85, evidence that correlates with impact to ABCD1 function (PP3). In summary, this variant meets the criteria to be classified as likely pathogenic for X-linked adrenoleukodystrophy based on the ACMG/AMP criteria applied, as specified by the ClinGen Peroxisomal Disorders VCEP: PS3_Supporting, PP4, PS4, PM2_Supporting, PP3 (ClinGen Peroxisomal Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ABCD1 Version 1.0.0)

ClinGen Evidence Repository → · reported verbatim, not re-tallied by Sugi Variant.

Computational evidence

Protein change
AlphaMissense	0.988	likely pathogenic ✓ concordant with ClinVar
REVEL	0.958	strongly pathogenic-leaning
SaProt	LLR -12.29	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 3,261 bp · p 4e-11 · regional, not allelic
Overall
CADD	26.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD1
Protein: p.Gln544Arg
Coding: c.1631A>G
dbSNP: rs2091763089
Type: single nucleotide variant
Location: chrX:153740234 (GRCh38)

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)

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-gln544arg (accessed [today's date]).

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