Is ARHGAP17 p.Pro715Ser (c.2143C>T) pathogenic?

ARHGAP17 p.Pro715Ser (c.2143C>T) is classified Uncertain significance in ARHGAP17 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-21). AlphaMissense: likely pathogenic (0.6548); Very rare (popmax 0.00226%, sas).

How common is ARHGAP17 p.Pro715Ser (c.2143C>T) in the general population?

ARHGAP17 p.Pro715Ser (c.2143C>T) is very rare (popmax 0.00226%, sas) (gnomAD).

What do computational predictors say about ARHGAP17 p.Pro715Ser (c.2143C>T)?

AlphaMissense predicts likely pathogenic (score 0.6548) — an in-silico prediction, not a clinical call.

ARHGAP17 p.Pro715Ser

c.2143C>T · rs2507572030 · VCV2212649

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6548 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00226%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6548	likely pathogenic
REVEL	0.231	benign-leaning
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.46 · regional, not allelic
Overall
CADD	22.8	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 0.00226% South Asian · 2/88,370 alleles

Filtering AF 0.000376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000141%

Overall 0.000138% 2/1,447,850 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.Pro715Ser
Coding: c.2143C>T
MANE Select: NM_001006634
dbSNP: rs2507572030
Type: single nucleotide variant
Location: chr16:24931156 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.82
Residue 715: 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-pro715ser (accessed [today's date]).

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