Is ARHGAP20 p.Ser5Phe (c.14C>T) pathogenic?

ARHGAP20 p.Ser5Phe (c.14C>T) is classified Uncertain significance in ARHGAP20 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely pathogenic (0.8674); Very rare (popmax 0.00436%, sas).

How common is ARHGAP20 p.Ser5Phe (c.14C>T) in the general population?

ARHGAP20 p.Ser5Phe (c.14C>T) is very rare (popmax 0.00436%, sas) (gnomAD).

What do computational predictors say about ARHGAP20 p.Ser5Phe (c.14C>T)?

AlphaMissense predicts likely pathogenic (score 0.8674) — an in-silico prediction, not a clinical call.

ARHGAP20 p.Ser5Phe

c.14C>T · VCV3938641

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8674 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00436%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8674	likely pathogenic · top 8% in ARHGAP20
REVEL	0.093	moderately benign-leaning
SaProt	LLR -8.30	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 7.7	GERP 0.78, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 121 kb · p 0.28 · regional, not allelic
Overall
CADD	22.9	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 0.00436% South Asian · 2/45,914 alleles

Filtering AF 0.000722% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00027%

Overall 0.000413% 5/1,211,820 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00436%	22,957
European (non-Finnish)	0.000286%	350,057

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.Ser5Phe
Coding: c.14C>T
MANE Select: NM_001384657
Type: single nucleotide variant
Location: chr11:110712218 (GRCh38)
Gene constraint: LOEUF 0.613 · pLI 0.07 (gnomAD)
Structure: AlphaFold pLDDT 55.05 · 1 PDB
Residue 5: the 'disordered' region

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

Similar variants

ARHGAP20 p.Ser5Pro Uncertain significance ★ ⚠ 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
ARHGAP20 p.Ala317Pro Uncertain significance ★ ⚠ same type
ARHGAP20 p.Ala41Pro 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-ser5phe (accessed [today's date]).

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