Is ARHGAP10 p.Pro646Ser (c.1936C>T) pathogenic?

ARHGAP10 p.Pro646Ser (c.1936C>T) is classified Uncertain significance in ARHGAP10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.0702); Absent from gnomAD v4.1.

How common is ARHGAP10 p.Pro646Ser (c.1936C>T) in the general population?

ARHGAP10 p.Pro646Ser (c.1936C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP10 p.Pro646Ser (c.1936C>T)?

AlphaMissense predicts likely benign (score 0.0702) — an in-silico prediction, not a clinical call.

ARHGAP10 p.Pro646Ser

c.1936C>T · VCV4132676

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0702 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0702	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.23	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 4.9	GERP 1.2, phastCons 1
Overall
CADD	17.75	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: ARHGAP10
Protein: p.Pro646Ser
Coding: c.1936C>T
MANE Select: NM_020824 · reported on NM_024605
Type: single nucleotide variant
Location: chr4:148046960 (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.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
ARHGAP21 p.Gly1121Ser 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-pro646ser (accessed [today's date]).

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