Is ARHGAP11A p.Pro366Leu (c.1097C>T) pathogenic?

ARHGAP11A p.Pro366Leu (c.1097C>T) is classified Uncertain significance in ARHGAP11A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely benign (0.2954); Ultra-rare (popmax 0.0395%, mid).

How common is ARHGAP11A p.Pro366Leu (c.1097C>T) in the general population?

ARHGAP11A p.Pro366Leu (c.1097C>T) is ultra-rare (popmax 0.0395%, mid) (gnomAD).

What do computational predictors say about ARHGAP11A p.Pro366Leu (c.1097C>T)?

AlphaMissense predicts likely benign (score 0.2954) — an in-silico prediction, not a clinical call.

ARHGAP11A p.Pro366Leu

c.1097C>T · VCV3421411

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2954 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0395%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2954	likely benign
REVEL	0.706	pathogenic-leaning
SaProt	LLR -9.07	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	Δ0.25	donor loss · deltas
Constraint at this position
Conservation	phyloP 7.3	phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 5,483 bp · p 4e-06 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0395% Middle Eastern · 2/5,058 alleles

Filtering AF 0.0224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0193%

Overall 0.00312% 50/1,603,870 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0395%	2,529
South Asian	0.0315%	3,170
Remaining individualsnot grpmax-eligible	0.00483%	20,684
African / African-American	0.00404%	24,771
Finnishnot grpmax-eligible	0.00313%	31,961
East Asian	0.00224%	44,662
European (non-Finnish)	0.000935%	106,963

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.Pro366Leu
Coding: c.1097C>T
MANE Select: NM_014783
Type: single nucleotide variant
Location: chr15:32629754 (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.Pro366= Benign ★★ 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-pro366leu (accessed [today's date]).

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