Is ARHGAP33 p.Pro329Ser (c.985C>T) pathogenic?

ARHGAP33 p.Pro329Ser (c.985C>T) is classified Uncertain significance in ARHGAP33 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). Absent from gnomAD v4.1.

How common is ARHGAP33 p.Pro329Ser (c.985C>T) in the general population?

ARHGAP33 p.Pro329Ser (c.985C>T) is absent from gnomAD v4.1 (gnomAD).

ARHGAP33 p.Pro329Ser

c.985C>T · VCV3940627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.662	pathogenic-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 3,835 bp · p 6.8e-11 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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: ARHGAP33
Protein: p.Pro329Ser
Coding: c.985C>T
MANE Select: NM_001366178
Type: single nucleotide variant
Location: chr19:35781152 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.54
Residue 329: the rho-gap domain

Full ARHGAP33 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARHGAP33 p.Leu422= Benign ★★ same type
ARHGAP33 p.Thr544= Benign ★★ same type
ARHGAP33 p.Ala1159Val Uncertain significance ★ same type
ARHGAP33 p.Ala1212Val Uncertain significance ★ same type
ARHGAP33 p.Ala461Thr Uncertain significance ★ same type
ARHGAP33 p.Ala486Val Uncertain significance ★ same type
ARHGAP33 p.Ala617Gly Uncertain significance ★ same type
ARHGAP33 p.Ala647Thr 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/arhgap33-p-pro329ser (accessed [today's date]).

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