Is ARHGAP17 p.Pro636His (c.1907C>A) pathogenic?

ARHGAP17 p.Pro636His (c.1907C>A) is classified Uncertain significance in ARHGAP17 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-05). AlphaMissense: likely pathogenic (0.5808); Ultra-rare (popmax 0.0617%, afr).

How common is ARHGAP17 p.Pro636His (c.1907C>A) in the general population?

ARHGAP17 p.Pro636His (c.1907C>A) is ultra-rare (popmax 0.0617%, afr) (gnomAD).

What do computational predictors say about ARHGAP17 p.Pro636His (c.1907C>A)?

AlphaMissense predicts likely pathogenic (score 0.5808) — an in-silico prediction, not a clinical call.

ARHGAP17 p.Pro636His

c.1907C>A · rs370592030 · VCV2600834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5808 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0617%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5808	likely pathogenic
REVEL	0.091	moderately benign-leaning
SaProt	LLR -10.68	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 9.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.46 · regional, not allelic
Overall
CADD	26.4	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 0.0617% African / African-American · 44/71,306 alleles

Filtering AF 0.0472% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0421%

Overall 0.00318% 48/1,507,322 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0617%	1,621
Middle Eastern	0.0194%	5,142
Admixed American	0.00475%	21,055
Remaining individualsnot grpmax-eligible	0.00173%	57,772

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.Pro636His
Coding: c.1907C>A
MANE Select: NM_001006634
dbSNP: rs370592030
Type: single nucleotide variant
Location: chr16:24931392 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.82
Residue 636: 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-pro636his (accessed [today's date]).

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