Is ARHGAP20 p.Ser20Phe (c.59C>T) pathogenic?

ARHGAP20 p.Ser20Phe (c.59C>T) is classified Uncertain significance in ARHGAP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely pathogenic (0.6185); Absent from gnomAD v4.1.

How common is ARHGAP20 p.Ser20Phe (c.59C>T) in the general population?

ARHGAP20 p.Ser20Phe (c.59C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP20 p.Ser20Phe (c.59C>T)?

AlphaMissense predicts likely pathogenic (score 0.6185) — an in-silico prediction, not a clinical call.

ARHGAP20 p.Ser20Phe

c.59C>T · rs1950679489 · VCV2491305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6185 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,369,556)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6185	likely pathogenic
REVEL	0.074	moderately benign-leaning
SaProt	LLR -9.57	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.94, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 121 kb · p 0.28 · regional, not allelic
Overall
CADD	23.6	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

No allele count reported in gnomAD v4.1 (AN 1,369,556). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARHGAP20
Protein: p.Ser20Phe
Coding: c.59C>T
MANE Select: NM_001384657
dbSNP: rs1950679489
Type: single nucleotide variant
Location: chr11:110712173 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 55.05 · 1 PDB
Residue 20: the 'disordered' region

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-ser20phe (accessed [today's date]).

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