Is ARHGAP20 p.Arg103Gln (c.308G>A) pathogenic?

ARHGAP20 p.Arg103Gln (c.308G>A) is classified Uncertain significance in ARHGAP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely pathogenic (0.8957); Very rare (popmax 0.00133%, afr).

How common is ARHGAP20 p.Arg103Gln (c.308G>A) in the general population?

ARHGAP20 p.Arg103Gln (c.308G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ARHGAP20 p.Arg103Gln (c.308G>A)?

AlphaMissense predicts likely pathogenic (score 0.8957) — an in-silico prediction, not a clinical call.

ARHGAP20 p.Arg103Gln

c.308G>A · VCV3938540

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8957 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8957	likely pathogenic · top 7% in ARHGAP20
REVEL	0.29	benign-leaning
SaProt	LLR -12.36	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 0.92, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 121 kb · p 0.28 · regional, not allelic
Overall
CADD	27.5	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 0.00133% African / African-American · 1/75,004 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000616% 9/1,461,800 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,004
European (non-Finnish)	0.000678%	147,494

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.Arg103Gln
Coding: c.308G>A
MANE Select: NM_001384657
Type: single nucleotide variant
Location: chr11:110630673 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 55.05 · 1 PDB
Residue 103: the ph domain

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

Similar variants

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ARHGAP20 p.Ala1077Gly Uncertain significance ★ ⚠ same type
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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
ARHGAP20 p.Ala41Pro 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-arg103gln (accessed [today's date]).

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