Is ARHGAP33 p.Pro261= (c.783C>T) pathogenic?

ARHGAP33 p.Pro261= (c.783C>T) is classified Likely benign in ARHGAP33 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-01). Ultra-rare (popmax 0.0187%, sas).

How common is ARHGAP33 p.Pro261= (c.783C>T) in the general population?

ARHGAP33 p.Pro261= (c.783C>T) is ultra-rare (popmax 0.0187%, sas) (gnomAD).

ARHGAP33 p.Pro261=

c.783C>T · rs760129805 · VCV2649756

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.11	GERP -3.8
Overall
CADD	4.559	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% South Asian · 17/91,080 alleles

Filtering AF 0.0118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00976%

Overall 0.00116% 17/1,461,650 alleles · ultra-rare

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: ARHGAP33
Protein: p.Pro261=
Coding: c.783C>T
MANE Select: NM_001366178
dbSNP: rs760129805
Type: single nucleotide variant
Location: chr19:35780770 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.54

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-pro261 (accessed [today's date]).

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