Is ARHGAP31 p.Pro1098Arg (c.3293C>G) pathogenic?

ARHGAP31 p.Pro1098Arg (c.3293C>G) is classified Uncertain significance in ARHGAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely benign (0.0901); Absent from gnomAD v4.1.

How common is ARHGAP31 p.Pro1098Arg (c.3293C>G) in the general population?

ARHGAP31 p.Pro1098Arg (c.3293C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP31 p.Pro1098Arg (c.3293C>G)?

AlphaMissense predicts likely benign (score 0.0901) — an in-silico prediction, not a clinical call.

ARHGAP31 p.Pro1098Arg

c.3293C>G · rs2472877866 · VCV2826317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0901 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0901	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.14	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 0.22	GERP -1.4
Regional constraint	o/e 0.88	unconstrained · MANE · 121 kb · p 1.9e-07 · regional, not allelic
Overall
CADD	13.75	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP31
Protein: p.Pro1098Arg
Coding: c.3293C>G
MANE Select: NM_020754
dbSNP: rs2472877866
Type: single nucleotide variant
Location: chr3:119415222 (GRCh38)
Gene constraint: LOEUF 0.38 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 43.32
Residue 1098: the 'disordered' region

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-pro1098arg (accessed [today's date]).

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