Is ARHGAP42 p.Ser817Phe (c.2450C>T) pathogenic?

ARHGAP42 p.Ser817Phe (c.2450C>T) is classified Uncertain significance in ARHGAP42 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-02). AlphaMissense: likely benign (0.0831); Absent from gnomAD v4.1.

How common is ARHGAP42 p.Ser817Phe (c.2450C>T) in the general population?

ARHGAP42 p.Ser817Phe (c.2450C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP42 p.Ser817Phe (c.2450C>T)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

ARHGAP42 p.Ser817Phe

c.2450C>T · rs904495849 · VCV3128868

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -9.37	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 3.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 15 kb · p 0.0013 · regional, not allelic
Overall
CADD	21.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ARHGAP42
Protein: p.Ser817Phe
Coding: c.2450C>T
MANE Select: NM_152432
dbSNP: rs904495849
Type: single nucleotide variant
Location: chr11:100979043 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.04
Residue 817: the sh3 domain

Full ARHGAP42 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP42 c.*3518A>G Uncertain significance ★ same type
ARHGAP42 c.*3523T>C Uncertain significance ★ same type
ARHGAP42 c.*3551G>T Uncertain significance ★ same type
ARHGAP42 c.*3554C>T Uncertain significance ★ same type
ARHGAP42 c.*3572A>C Uncertain significance ★ same type
ARHGAP42 c.*3622C>T Uncertain significance ★ same type
ARHGAP42 c.*3632A>T Uncertain significance ★ same type
ARHGAP42 c.*3634A>C 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/arhgap42-p-ser817phe (accessed [today's date]).

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