ARHGAP33 p.Pro252Gln
c.755C>A · rs145164586 · VCV3128795
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00512%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.098 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.8 | GERP 0.81, phastCons 1 |
| Regional constraint | o/e 0.68 | unconstrained · MANE · 3,835 bp · p 6.8e-11 · regional, not allelic |
| Overall | ||
| CADD | 20.5 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00512%
African / African-American · 3/58,558 alleles
Filtering AF
0.00209%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00182%
Overall
0.00269%
36/1,338,284 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00512% | 19,519 |
| European (non-Finnish) | 0.00295% | 33,876 |
| Finnishnot grpmax-eligible | 0.00267% | 37,412 |
| Remaining individualsnot grpmax-eligible | 0.00219% | 45,744 |
| Admixed American | 0.00213% | 47,050 |
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.Pro252Gln
- Coding
- c.755C>A
- MANE Select
- NM_001366178
- dbSNP
- rs145164586
- Type
- single nucleotide variant
- Location
- chr19:35780634 (GRCh38)
- Gene constraint
- LOEUF 0.59 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.54
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-pro252gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown