Is ARHGAP17 p.Ile379Phe (c.1135A>T) pathogenic?

ARHGAP17 p.Ile379Phe (c.1135A>T) is classified Uncertain significance in ARHGAP17 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-18). AlphaMissense: likely pathogenic (0.8046); Absent from gnomAD v4.1.

How common is ARHGAP17 p.Ile379Phe (c.1135A>T) in the general population?

ARHGAP17 p.Ile379Phe (c.1135A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP17 p.Ile379Phe (c.1135A>T)?

AlphaMissense predicts likely pathogenic (score 0.8046) — an in-silico prediction, not a clinical call.

ARHGAP17 p.Ile379Phe

c.1135A>T · rs2507829365 · VCV2290086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8046 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8046	likely pathogenic
REVEL	0.313	indeterminate
SaProt	LLR -10.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 76 kb · p 1.8e-08 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP17
Protein: p.Ile379Phe
Coding: c.1135A>T
MANE Select: NM_001006634
dbSNP: rs2507829365
Type: single nucleotide variant
Location: chr16:24947588 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.82
Residue 379: 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-ile379phe (accessed [today's date]).

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