Is ARHGAP20 p.Val596Ile (c.1786G>A) pathogenic?

ARHGAP20 p.Val596Ile (c.1786G>A) is classified Uncertain significance in ARHGAP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). AlphaMissense: likely benign (0.0823); Ultra-rare (popmax 0.0626%, sas).

How common is ARHGAP20 p.Val596Ile (c.1786G>A) in the general population?

ARHGAP20 p.Val596Ile (c.1786G>A) is ultra-rare (popmax 0.0626%, sas) (gnomAD).

What do computational predictors say about ARHGAP20 p.Val596Ile (c.1786G>A)?

AlphaMissense predicts likely benign (score 0.0823) — an in-silico prediction, not a clinical call.

ARHGAP20 p.Val596Ile

c.1786G>A · rs563325668 · VCV2242865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0823 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0626%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0823	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.75	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 0.39	GERP 0.56
Regional constraint	o/e 0.72	unconstrained · MANE · 9,833 bp · p 8.8e-07 · regional, not allelic
Overall
CADD	14.94	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 0.0626% South Asian · 57/91,082 alleles

Filtering AF 0.0496% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0449%

Overall 0.00378% 61/1,614,188 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0626%	1,598
Remaining individualsnot grpmax-eligible	0.0048%	20,836
European (non-Finnish)	8.47e-05%	1,180,018

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: ARHGAP20
Protein: p.Val596Ile
Coding: c.1786G>A
MANE Select: NM_001384657
dbSNP: rs563325668
Type: single nucleotide variant
Location: chr11:110581160 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 55.05 · 1 PDB

Full ARHGAP20 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP20 p.Ala1056Gly Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala1077Gly Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala202Thr Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala222Val Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala316Thr Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala317Pro Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala41Pro Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala689Val 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/arhgap20-p-val596ile (accessed [today's date]).

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