Is ABCD1 p.Arg591Gln (c.1772G>A) pathogenic?

ABCD1 p.Arg591Gln (c.1772G>A) is classified Pathogenic/Likely pathogenic in ABCD1 (ClinVar, Multiple submitters, 14 submitters; last evaluated 2026-01-23). AlphaMissense: likely pathogenic (0.7193); Very rare (popmax 0.000112%, nfe); Associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1.

What condition is associated with ABCD1 p.Arg591Gln (c.1772G>A)?

ABCD1 p.Arg591Gln (c.1772G>A) is associated with Ehlers-Danlos syndrome, kyphoscoliotic type 1, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg591Gln (c.1772G>A) in the general population?

ABCD1 p.Arg591Gln (c.1772G>A) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about ABCD1 p.Arg591Gln (c.1772G>A)?

AlphaMissense predicts likely pathogenic (score 0.7193) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg591Gln

c.1772G>A · rs1557054873 · VCV458635

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 14 submitters

AlphaMissense

likely pathogenic

0.7193 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Ehlers-Danlos syndrome, kyphoscoliotic type 1

Computational evidence

Protein change
AlphaMissense	0.7193	likely pathogenic ✓ concordant with ClinVar
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -13.52	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
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 0.38	unconstrained · MANE · 3,261 bp · p 4e-11 · regional, not allelic
Overall
CADD	26.6	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 0.000112% European (non-Finnish) · 1/895,440 alleles

Overall 9.12e-05% 1/1,096,262 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.Arg591Gln
Coding: c.1772G>A
MANE Select: NM_000033
dbSNP: rs1557054873
Type: single nucleotide variant
Location: chrX:153740711 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 591: a UniProt-annotated variant site (in ald); a UniProt-annotated variant site (in ald; amn-type; significantly decreases homodimerization and abolishes heterodimerization with abcd2 and abcd3); a turn; the abc transporter domain

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

Disease context

Ehlers-Danlos syndrome, kyphoscoliotic type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: adrenoleukodystrophy

Similar variants

ABCD1 p.Arg591Pro Likely pathogenic ★★ same residue
ABCD1 p.Arg591Trp Pathogenic/Likely pathogenic ★★ same residue
ABCD1 p.Arg591= 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-arg591gln (accessed [today's date]).

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