Is ARHGAP15 p.Pro192Thr (c.574C>A) pathogenic?

ARHGAP15 p.Pro192Thr (c.574C>A) is classified Uncertain significance in ARHGAP15 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely benign (0.1583); Ultra-rare (popmax 0.0156%, eas).

How common is ARHGAP15 p.Pro192Thr (c.574C>A) in the general population?

ARHGAP15 p.Pro192Thr (c.574C>A) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ARHGAP15 p.Pro192Thr (c.574C>A)?

AlphaMissense predicts likely benign (score 0.1583) — an in-silico prediction, not a clinical call.

ARHGAP15 p.Pro192Thr

c.574C>A · VCV3421543

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1583 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1583	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -12.10	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 613 kb · p 0.84 · regional, not allelic
Overall
CADD	15.8	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 0.0156% East Asian · 7/44,744 alleles

Filtering AF 0.00728% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00516%

Overall 0.000622% 10/1,606,990 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,392
Admixed American	0.00172%	58,294
South Asian	0.00112%	88,998
European (non-Finnish)	8.49e-05%	1,178,092

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: ARHGAP15
Protein: p.Pro192Thr
Coding: c.574C>A
MANE Select: NM_018460
Type: single nucleotide variant
Location: chr2:143436913 (GRCh38)
Gene constraint: LOEUF 1.134 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.31 · 1 PDB

Full ARHGAP15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP15 p.Pro192Arg Uncertain significance ★ ⚠ same residue
ARHGAP15 c.474+1G>A Uncertain significance ★ same type
ARHGAP15 p.Ala183Thr Uncertain significance ★ ⚠ same type
ARHGAP15 p.Ala242Thr Uncertain significance ★ ⚠ same type
ARHGAP15 p.Ala304Thr Uncertain significance ★ ⚠ same type
ARHGAP15 p.Arg18Cys Uncertain significance ★ ⚠ same type
ARHGAP15 p.Arg200Ser Uncertain significance ★ ⚠ same type
ARHGAP15 p.Arg250Gln 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/arhgap15-p-pro192thr (accessed [today's date]).

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