Is ARHGAP10 p.Arg491Pro (c.1472G>C) pathogenic?

ARHGAP10 p.Arg491Pro (c.1472G>C) is classified Uncertain significance in ARHGAP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). AlphaMissense: likely pathogenic (0.9851); Very rare (popmax 0.00345%, sas).

How common is ARHGAP10 p.Arg491Pro (c.1472G>C) in the general population?

ARHGAP10 p.Arg491Pro (c.1472G>C) is very rare (popmax 0.00345%, sas) (gnomAD).

What do computational predictors say about ARHGAP10 p.Arg491Pro (c.1472G>C)?

AlphaMissense predicts likely pathogenic (score 0.9851) — an in-silico prediction, not a clinical call.

ARHGAP10 p.Arg491Pro

c.1472G>C · rs755998386 · VCV3128469

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9851 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00345%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9851	likely pathogenic · top 7% in ARHGAP10
REVEL	0.758	pathogenic-leaning
SaProt	LLR -15.65	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 2.7, phastCons 1
Overall
CADD	28.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.00345% South Asian · 3/87,036 alleles

Filtering AF 0.000916% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000454%

Overall 0.000277% 4/1,444,986 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00345%	29,012
Ashkenazi Jewishnot grpmax-eligible	0.00344%	29,088

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: ARHGAP10
Protein: p.Arg491Pro
Coding: c.1472G>C
MANE Select: NM_020824 · reported on NM_024605
dbSNP: rs755998386
Type: single nucleotide variant
Location: chr4:147965045 (GRCh38)
Structure: AlphaFold pLDDT 45.03 · 3 PDB

Full ARHGAP10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP10 p.Arg491His Uncertain significance ★ ⚠ same residue
ARHGAP10 p.Asn222Ser Uncertain significance ★★ ⚠ same type
ARHGAP10 p.Ala405= Benign ★★ same type
ARHGAP10 p.Arg243= Benign ★★ same type
ARHGAP10 p.Ile676Val Likely benign ★★ same type
ARHGAP10 p.Ser487= Benign ★★ same type
ARHGAP10 p.Tyr614= Benign ★★ same type
ARHGAP21 p.Cys1016Ser Likely benign ★★ 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/arhgap10-p-arg491pro (accessed [today's date]).

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