Is ARHGAP17 p.Pro865Ser (c.2593C>T) pathogenic?

ARHGAP17 p.Pro865Ser (c.2593C>T) is classified Uncertain significance in ARHGAP17 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.082); Very rare (popmax 0.00314%, nfe).

How common is ARHGAP17 p.Pro865Ser (c.2593C>T) in the general population?

ARHGAP17 p.Pro865Ser (c.2593C>T) is very rare (popmax 0.00314%, nfe) (gnomAD).

What do computational predictors say about ARHGAP17 p.Pro865Ser (c.2593C>T)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

ARHGAP17 p.Pro865Ser

c.2593C>T · rs999318435 · VCV2213055

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00314%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.082	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -5.59	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 7.2	GERP 1, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.46 · regional, not allelic
Overall
CADD	20.1	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 0.00314% European (non-Finnish) · 37/1,180,036 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00229% 37/1,614,084 alleles · very rare

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.Pro865Ser
Coding: c.2593C>T
MANE Select: NM_001006634
dbSNP: rs999318435
Type: single nucleotide variant
Location: chr16:24920183 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.82
Residue 865: the 'disordered' region

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-pro865ser (accessed [today's date]).

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