Is ARHGAP17 p.Val320Ile (c.958G>A) pathogenic?

ARHGAP17 p.Val320Ile (c.958G>A) is classified Uncertain significance in ARHGAP17 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely benign (0.3038); Ultra-rare (popmax 0.0135%, nfe).

How common is ARHGAP17 p.Val320Ile (c.958G>A) in the general population?

ARHGAP17 p.Val320Ile (c.958G>A) is ultra-rare (popmax 0.0135%, nfe) (gnomAD).

What do computational predictors say about ARHGAP17 p.Val320Ile (c.958G>A)?

AlphaMissense predicts likely benign (score 0.3038) — an in-silico prediction, not a clinical call.

ARHGAP17 p.Val320Ile

c.958G>A · VCV4642144

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3038 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0135%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3038	likely benign
REVEL	0.169	moderately benign-leaning
SaProt	LLR -6.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 76 kb · p 1.8e-08 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0135% European (non-Finnish) · 159/1,179,830 alleles

Filtering AF 0.0117% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0111%

Overall 0.00991% 160/1,613,794 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0135%	7,420
Admixed American	0.00167%	59,978

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: ARHGAP17
Protein: p.Val320Ile
Coding: c.958G>A
MANE Select: NM_001006634
Type: single nucleotide variant
Location: chr16:24952937 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.82
Residue 320: the rho-gap domain

Full ARHGAP17 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP17 p.Arg630His Uncertain significance ★★ ⚠ same type
ARHGAP17 p.Ala142Thr Uncertain significance ★ ⚠ same type
ARHGAP17 p.Ala203Val Uncertain significance ★ ⚠ same type
ARHGAP17 p.Ala400Val Uncertain significance ★ ⚠ same type
ARHGAP17 p.Ala453Val Uncertain significance ★ ⚠ same type
ARHGAP17 p.Ala538Ser Uncertain significance ★ ⚠ same type
ARHGAP17 p.Ala538Thr Uncertain significance ★ ⚠ same type
ARHGAP17 p.Ala607Pro 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/arhgap17-p-val320ile (accessed [today's date]).

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