Is ARHGAP4 p.Ala804= (c.2412C>A) pathogenic?

ARHGAP4 p.Ala804= (c.2412C>A) is classified Likely benign in ARHGAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-01). Very rare (popmax 0.00192%, nfe).

How common is ARHGAP4 p.Ala804= (c.2412C>A) in the general population?

ARHGAP4 p.Ala804= (c.2412C>A) is very rare (popmax 0.00192%, nfe) (gnomAD).

ARHGAP4 p.Ala804=

c.2412C>A · rs782163114 · VCV2661750

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00192%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.001	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.9	GERP -3.4
Overall
CADD	0.067	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00192% European (non-Finnish) · 17/883,424 alleles

Filtering AF 0.00117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000958%

Overall 0.00143% 17/1,186,079 alleles · very rare exomes 17/1,072,213 · genomes 0/113,866 · joint denominator

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: ARHGAP4
Protein: p.Ala804=
Coding: c.2412C>A
MANE Select: NM_001666
dbSNP: rs782163114
Type: single nucleotide variant
Location: chrX:153909743 (GRCh38)
Structure: AlphaFold pLDDT 76.48 · 1 PDB
Residue 804: the sh3 domain

Full ARHGAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP4 p.Ala804Asp Uncertain significance ★ ⚠ same residue
ARHGAP4 p.Ala804Ser Uncertain significance ★ ⚠ same residue
ARHGAP4 p.Ala804Thr Uncertain significance ★ ⚠ same residue
ARHGAP4 p.Val705Ile Uncertain significance ★★ ⚠ same type
ARHGAP4 c.2415-4G>A Benign ★★ same type
ARHGAP4 c.2608-6C>T Benign ★★ same type
ARHGAP4 p.Asp420= Benign ★★ same type
ARHGAP4 p.His572= 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/arhgap4-p-ala804 (accessed [today's date]).

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