Is ARHGAP11A p.Arg400= (c.1200G>A) pathogenic?

ARHGAP11A p.Arg400= (c.1200G>A) is classified Benign in ARHGAP11A (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-06-12). Common (popmax 6.37%, afr) — too common for a highly-penetrant pathogenic allele.

ARHGAP11A p.Arg400=

Q: How common is ARHGAP11A p.Arg400= (c.1200G>A) in the general population?

ARHGAP11A p.Arg400= (c.1200G>A) is common (popmax 6.37%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1200G>A · rs61733063 · VCV781158

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.37%, 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 0.54	phastCons 0.99
Overall
CADD	7.609	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.37% African / African-American · 4,778/75,004 alleles

Filtering AF 6.22% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.16%

Overall 0.335% 5,406/1,614,048 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.37%	16
Remaining individualsnot grpmax-eligible	0.422%	237
Admixed American	0.415%	241
Middle Eastern	0.28%	357
South Asian	0.0209%	4,794
European (non-Finnish)	0.0067%	14,936

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.Arg400=
Coding: c.1200G>A
MANE Select: NM_014783
dbSNP: rs61733063
Type: single nucleotide variant
Location: chr15:32633073 (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.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
ARHGAP11A p.Ala251Ser 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-arg400 (accessed [today's date]).

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