Is ARHGAP20 p.Ser343Cys (c.1028C>G) pathogenic?

ARHGAP20 p.Ser343Cys (c.1028C>G) is classified Uncertain significance in ARHGAP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-07). AlphaMissense: likely benign (0.1119); Absent from gnomAD v4.1.

How common is ARHGAP20 p.Ser343Cys (c.1028C>G) in the general population?

ARHGAP20 p.Ser343Cys (c.1028C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP20 p.Ser343Cys (c.1028C>G)?

AlphaMissense predicts likely benign (score 0.1119) — an in-silico prediction, not a clinical call.

ARHGAP20 p.Ser343Cys

c.1028C>G · VCV4642185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1119 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1119	likely benign
REVEL	0.326	indeterminate
SaProt	LLR -11.09	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 121 kb · p 0.28 · regional, not allelic
Overall
CADD	23.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP20
Protein: p.Ser343Cys
Coding: c.1028C>G
MANE Select: NM_001384657
Type: single nucleotide variant
Location: chr11:110592092 (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-ser343cys (accessed [today's date]).

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