Is ABCD1 p.Arg191His (c.572G>A) pathogenic?

ABCD1 p.Arg191His (c.572G>A) is classified Likely benign in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-15). AlphaMissense: likely benign (0.1124); Very rare (popmax 0.00526%, sas); Associated with adrenoleukodystrophy.

What condition is associated with ABCD1 p.Arg191His (c.572G>A)?

ABCD1 p.Arg191His (c.572G>A) is associated with adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Arg191His (c.572G>A) in the general population?

ABCD1 p.Arg191His (c.572G>A) is very rare (popmax 0.00526%, sas) (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.Arg191His (c.572G>A)?

AlphaMissense predicts likely benign (score 0.1124) — an in-silico prediction, not a clinical call.

ABCD1 p.Arg191His

c.572G>A · rs1373052080 · VCV1984027

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00526%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

adrenoleukodystrophy

Computational evidence

Protein change
AlphaMissense	0.1124	likely benign
REVEL	0.591	indeterminate
SaProt	LLR -7.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP -0.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	24.8	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 0.00526% South Asian · 3/56,987 alleles

Filtering AF 0.0014% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000687%

Overall 0.000826% 10/1,211,008 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00526%	18,996
Admixed American	0.00434%	23,027
Remaining individualsnot grpmax-eligible	0.0021%	47,614
European (non-Finnish)	0.000447%	223,876

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.Arg191His
Coding: c.572G>A
MANE Select: NM_000033
dbSNP: rs1373052080
Type: single nucleotide variant
Location: chrX:153725838 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 191: a β-strand; 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.Arg191Cys Uncertain significance ★★ ⚠ same residue
ABCD1 p.Arg191= 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
ABCD1 c.1866-2A>T 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-arg191his (accessed [today's date]).

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