Is ABCD1 p.Arg711Gln (c.2132G>A) pathogenic?

ABCD1 p.Arg711Gln (c.2132G>A) is classified Uncertain significance in ABCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-30). AlphaMissense: likely benign (0.0544); Very rare (popmax 0.00928%, eas); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Arg711Gln (c.2132G>A)?

ABCD1 p.Arg711Gln (c.2132G>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg711Gln (c.2132G>A) in the general population?

ABCD1 p.Arg711Gln (c.2132G>A) is very rare (popmax 0.00928%, eas) (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.Arg711Gln (c.2132G>A)?

AlphaMissense predicts likely benign (score 0.0544) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg711Gln

c.2132G>A · rs781886493 · VCV2713076

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0544 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00928%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
AlphaMissense	0.0544	likely benign
REVEL	0.214	benign-leaning
SaProt	LLR -5.26	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.11	GERP -3.5, phastCons 0.59
Regional constraint	o/e 0.70	unconstrained · MANE · 242 bp · p 0.011 · regional, not allelic
Overall
CADD	9.179	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00928% East Asian · 3/32,313 alleles

Filtering AF 0.00246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00128%

Overall 0.0011% 13/1,186,133 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00928%	10,771
South Asian	0.00185%	54,011
European (non-Finnish)	0.00102%	98,241

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.Arg711Gln
Coding: c.2132G>A
MANE Select: NM_000033
dbSNP: rs781886493
Type: single nucleotide variant
Location: chrX:153743629 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 711: the 'required for homodimerization' region; an α-helix

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.Arg711Trp Uncertain significance ★★ ⚠ 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
ABCD1 c.1866-2A>T Likely pathogenic ★★ same condition
ABCD1 c.901-1G>A 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-arg711gln (accessed [today's date]).

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