Is ARHGAP1 p.Phe370Ser (c.1109T>C) pathogenic?

ARHGAP1 p.Phe370Ser (c.1109T>C) is classified Uncertain significance in ARHGAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-08). AlphaMissense: likely pathogenic (0.6956); Ultra-rare (popmax 0.0986%, mid).

How common is ARHGAP1 p.Phe370Ser (c.1109T>C) in the general population?

ARHGAP1 p.Phe370Ser (c.1109T>C) is ultra-rare (popmax 0.0986%, mid) (gnomAD).

What do computational predictors say about ARHGAP1 p.Phe370Ser (c.1109T>C)?

AlphaMissense predicts likely pathogenic (score 0.6956) — an in-silico prediction, not a clinical call.

ARHGAP1 p.Phe370Ser

c.1109T>C · VCV3421136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6956 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0986%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6956	likely pathogenic
REVEL	0.268	benign-leaning
SaProt	LLR -11.78	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.3	GERP 1.6, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 17 kb · p 0.00064 · regional, not allelic
Overall
CADD	26.8	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 0.0986% Middle Eastern · 6/6,084 alleles

Filtering AF 0.0429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00235% 38/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0986%	1,014
Remaining individualsnot grpmax-eligible	0.0064%	15,622
African / African-American	0.004%	24,978
European (non-Finnish)	0.00212%	47,201

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: ARHGAP1
Protein: p.Phe370Ser
Coding: c.1109T>C
MANE Select: NM_004308
Type: single nucleotide variant
Location: chr11:46679387 (GRCh38)
Gene constraint: LOEUF 0.601 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 82.64 · 11 PDB
Residue 370: the rho-gap domain; an α-helix

Full ARHGAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP1 p.Leu263Phe Benign ★★ same type
ARHGAP1 p.Pro52= Benign ★★ same type
ARHGAP1 p.Ala225Ser Uncertain significance ★ ⚠ same type
ARHGAP1 p.Ala26Val Uncertain significance ★ ⚠ same type
ARHGAP1 p.Ala373Thr Uncertain significance ★ ⚠ same type
ARHGAP1 p.Ala68Pro Uncertain significance ★ ⚠ same type
ARHGAP1 p.Arg234Gln Uncertain significance ★ ⚠ same type
ARHGAP1 p.Arg234Trp 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/arhgap1-p-phe370ser (accessed [today's date]).

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