Is ARHGAP31 p.Arg151Gln (c.452G>A) pathogenic?

ARHGAP31 p.Arg151Gln (c.452G>A) is classified Conflicting classifications of pathogenicity in ARHGAP31 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-04-08). AlphaMissense: likely benign (0.0855); Rare (popmax 0.288%, afr).

How common is ARHGAP31 p.Arg151Gln (c.452G>A) in the general population?

ARHGAP31 p.Arg151Gln (c.452G>A) is rare (popmax 0.288%, afr) (gnomAD).

What do computational predictors say about ARHGAP31 p.Arg151Gln (c.452G>A)?

AlphaMissense predicts likely benign (score 0.0855) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Arg151Gln

c.452G>A · rs201519981 · VCV499152

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0855 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.288%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0855	likely benign
REVEL	0.132	moderately benign-leaning
SaProt	LLR -10.62	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	27.8	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 0.288% African / African-American · 216/74,968 alleles

Filtering AF 0.257% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.244%

Overall 0.0157% 253/1,613,988 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.288%	347
Remaining individualsnot grpmax-eligible	0.0208%	4,808
Middle Eastern	0.0165%	6,062
Admixed American	0.00833%	12,000
South Asian	0.00659%	15,177
Finnishnot grpmax-eligible	0.00156%	64,008
European (non-Finnish)	0.000932%	107,272

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: ARHGAP31
Protein: p.Arg151Gln
Coding: c.452G>A
MANE Select: NM_020754
dbSNP: rs201519981
Type: single nucleotide variant
Location: chr3:119382312 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 151: the rho-gap domain

Full ARHGAP31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP31 p.Ala18Val Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Ala634Asp Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg1377Ser Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg199Gln Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg256Cys Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg426Gly Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg478His Uncertain significance ★★ ⚠ same type
ARHGAP31 p.Arg510Ser Uncertain significance ★★ ⚠ same type

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/arhgap31-p-arg151gln (accessed [today's date]).

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