Is ARHGAP11A p.Pro366= (c.1098G>A) pathogenic?

ARHGAP11A p.Pro366= (c.1098G>A) is classified Benign in ARHGAP11A (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-07-06). Common (popmax 5.82%, afr) — too common for a highly-penetrant pathogenic allele.

ARHGAP11A p.Pro366=

Q: How common is ARHGAP11A p.Pro366= (c.1098G>A) in the general population?

ARHGAP11A p.Pro366= (c.1098G>A) is common (popmax 5.82%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1098G>A · rs181899708 · VCV781157

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 5.82%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	phastCons 1
Overall
CADD	12.67	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.82% African / African-American · 4,279/73,528 alleles

Filtering AF 5.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.61%

Overall 0.301% 4,820/1,599,698 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.82%	17
Admixed American	0.383%	261
Remaining individualsnot grpmax-eligible	0.359%	279
Middle Eastern	0.222%	450
South Asian	0.0182%	5,497
European (non-Finnish)	0.00613%	16,324

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: ARHGAP11A
Protein: p.Pro366=
Coding: c.1098G>A
MANE Select: NM_014783
dbSNP: rs181899708
Type: single nucleotide variant
Location: chr15:32629755 (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 p.Pro366Leu Uncertain significance ★ ⚠ same residue
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.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-pro366 (accessed [today's date]).

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