Is ARHGAP11A p.Pro524Ser (c.1570C>T) pathogenic?

ARHGAP11A p.Pro524Ser (c.1570C>T) is classified Uncertain significance in ARHGAP11A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely benign (0.1174); Absent from gnomAD v4.1.

How common is ARHGAP11A p.Pro524Ser (c.1570C>T) in the general population?

ARHGAP11A p.Pro524Ser (c.1570C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP11A p.Pro524Ser (c.1570C>T)?

AlphaMissense predicts likely benign (score 0.1174) — an in-silico prediction, not a clinical call.

ARHGAP11A p.Pro524Ser

c.1570C>T · VCV3421450

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1174 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1174	likely benign
REVEL	0.104	moderately benign-leaning
SaProt	LLR -4.05	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 3.9	phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 8,081 bp · p 0.57 · regional, not allelic
Overall
CADD	21.6	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: ARHGAP11A
Protein: p.Pro524Ser
Coding: c.1570C>T
MANE Select: NM_014783
Type: single nucleotide variant
Location: chr15:32636343 (GRCh38)
Gene constraint: LOEUF 0.8 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.52 · 1 PDB

Full ARHGAP11A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP11A c.1235+5T>G Benign ★★ same type
ARHGAP11A p.Arg400= Benign ★★ same type
ARHGAP11A p.Asn978= Benign ★★ same type
ARHGAP11A p.Gln903= Benign ★★ same type
ARHGAP11A p.Pro366= Benign ★★ same type
ARHGAP11A p.Ala112Ser Uncertain significance ★ ⚠ same type
ARHGAP11A p.Ala112Val Uncertain significance ★ ⚠ same type
ARHGAP11A p.Ala235Thr 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/arhgap11a-p-pro524ser (accessed [today's date]).

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