Is ARHGAP28 p.Ser167Pro (c.499T>C) pathogenic?

ARHGAP28 p.Ser167Pro (c.499T>C) is classified Uncertain significance in ARHGAP28 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-08). AlphaMissense: likely benign (0.057); Absent from gnomAD v4.1.

How common is ARHGAP28 p.Ser167Pro (c.499T>C) in the general population?

ARHGAP28 p.Ser167Pro (c.499T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ARHGAP28 p.Ser167Pro (c.499T>C)?

AlphaMissense predicts likely benign (score 0.057) — an in-silico prediction, not a clinical call.

ARHGAP28 p.Ser167Pro

c.499T>C · VCV3422568

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.057 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.057	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -8.61	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 -0.69	GERP -5.5
Regional constraint	o/e 0.96	unconstrained · MANE · 182 kb · p 0.29 · regional, not allelic
Overall
CADD	0.643	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: ARHGAP28
Protein: p.Ser167Pro
Coding: c.499T>C
MANE Select: NM_001366230
Type: single nucleotide variant
Location: chr18:6837370 (GRCh38)
Gene constraint: LOEUF 0.796 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.63

Full ARHGAP28 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP28 p.Cys683Tyr Benign ★★ same type
ARHGAP28 p.Ala268Val Uncertain significance ★ ⚠ same type
ARHGAP28 p.Ala283Thr Uncertain significance ★ ⚠ same type
ARHGAP28 p.Ala357Val Uncertain significance ★ ⚠ same type
ARHGAP28 p.Ala502Glu Uncertain significance ★ ⚠ same type
ARHGAP28 p.Ala502Val Uncertain significance ★ ⚠ same type
ARHGAP28 p.Ala707Ser Uncertain significance ★ ⚠ same type
ARHGAP28 p.Ala707Val 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/arhgap28-p-ser167pro (accessed [today's date]).

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