Is ARHGAP31 p.Pro508Gln (c.1523C>A) pathogenic?

ARHGAP31 p.Pro508Gln (c.1523C>A) is classified Likely benign in ARHGAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely pathogenic (0.8617); Rare (popmax 0.218%, sas); Associated with Inborn genetic diseases.

What condition is associated with ARHGAP31 p.Pro508Gln (c.1523C>A)?

ARHGAP31 p.Pro508Gln (c.1523C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ARHGAP31 p.Pro508Gln (c.1523C>A) in the general population?

ARHGAP31 p.Pro508Gln (c.1523C>A) is rare (popmax 0.218%, sas) (gnomAD).

What do computational predictors say about ARHGAP31 p.Pro508Gln (c.1523C>A)?

AlphaMissense predicts likely pathogenic (score 0.8617) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Pro508Gln

c.1523C>A · VCV3890915

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8617 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.218%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8617	likely pathogenic
REVEL	0.2	benign-leaning
SaProt	LLR -9.59	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.7, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	27.7	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 0.218% South Asian · 199/91,088 alleles

Filtering AF 0.194% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.184%

Overall 0.0129% 208/1,614,276 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.218%	458
Remaining individualsnot grpmax-eligible	0.0112%	8,930
Admixed American	0.00167%	60,034
European (non-Finnish)	8.47e-05%	1,180,058

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.Pro508Gln
Coding: c.1523C>A
MANE Select: NM_020754
Type: single nucleotide variant
Location: chr3:119402275 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 508: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARHGAP31 p.Ala18Val Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Ala634Asp Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg1377Ser Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg199Gln Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg256Cys Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg478His Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg510Ser Uncertain significance ★★ ⚠ same condition
ARHGAP31 p.Arg950Cys Uncertain significance ★★ ⚠ 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/arhgap31-p-pro508gln (accessed [today's date]).

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