Is ARHGAP20 p.Arg855Pro (c.2564G>C) pathogenic?

ARHGAP20 p.Arg855Pro (c.2564G>C) is classified Uncertain significance in ARHGAP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely benign (0.232); Ultra-rare (popmax 0.024%, afr).

How common is ARHGAP20 p.Arg855Pro (c.2564G>C) in the general population?

ARHGAP20 p.Arg855Pro (c.2564G>C) is ultra-rare (popmax 0.024%, afr) (gnomAD).

What do computational predictors say about ARHGAP20 p.Arg855Pro (c.2564G>C)?

AlphaMissense predicts likely benign (score 0.232) — an in-silico prediction, not a clinical call.

ARHGAP20 p.Arg855Pro

c.2564G>C · VCV3938619

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.232 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.232	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.95	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 0.58	GERP -2.3, phastCons 0.21
Regional constraint	o/e 1.01	unconstrained · MANE · 1,589 bp · p 0.87 · regional, not allelic
Overall
CADD	6.451	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 0.024% African / African-American · 18/74,934 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00112% 18/1,614,102 alleles · ultra-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: ARHGAP20
Protein: p.Arg855Pro
Coding: c.2564G>C
MANE Select: NM_001384657
Type: single nucleotide variant
Location: chr11:110580382 (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.Arg855His Uncertain significance ★ ⚠ same residue
ARHGAP20 p.Arg855Leu Uncertain significance ★ ⚠ same residue
ARHGAP20 p.Arg855Cys Likely benign ★ ⚠ same residue
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

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-arg855pro (accessed [today's date]).

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