Is ARHGAP20 p.Arg671Trp (c.2011C>T) pathogenic?

ARHGAP20 p.Arg671Trp (c.2011C>T) is classified Uncertain significance in ARHGAP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.089); Ultra-rare (popmax 0.0227%, afr).

How common is ARHGAP20 p.Arg671Trp (c.2011C>T) in the general population?

ARHGAP20 p.Arg671Trp (c.2011C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

What do computational predictors say about ARHGAP20 p.Arg671Trp (c.2011C>T)?

AlphaMissense predicts likely benign (score 0.089) — an in-silico prediction, not a clinical call.

ARHGAP20 p.Arg671Trp

c.2011C>T · rs369212996 · VCV2390007

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.089 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.089	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -8.67	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 1.8	GERP -1.3, phastCons 0.012
Regional constraint	o/e 1.01	unconstrained · MANE · 1,589 bp · p 0.87 · regional, not allelic
Overall
CADD	20.8	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 0.0227% African / African-American · 17/74,926 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00297% 48/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,407
Remaining individualsnot grpmax-eligible	0.0128%	7,810
Admixed American	0.0117%	8,573
South Asian	0.0022%	45,545
European (non-Finnish)	0.00119%	84,280

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.Arg671Trp
Coding: c.2011C>T
MANE Select: NM_001384657
dbSNP: rs369212996
Type: single nucleotide variant
Location: chr11:110580935 (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

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ARHGAP20 p.Ala222Val Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala316Thr Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala317Pro Uncertain significance ★ ⚠ same type
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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-arg671trp (accessed [today's date]).

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