ARHGAP33 p.Pro73Ser
c.217C>T · VCV3423486
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.037 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 3.9 | GERP 1.2, phastCons 1 |
| Regional constraint | o/e 0.88 | unconstrained · MANE · 2,859 bp · p 0.16 · regional, not allelic |
| Overall | ||
| CADD | 18.95 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,898 alleles
Filtering AF
2.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1e-05%
Overall
0.000186%
3/1,614,070 alleles · very rare
exomes 2/1,461,874 · genomes 1/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,898 |
| European (non-Finnish) | 0.000169% | 590,019 |
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.Pro73Ser
- Coding
- c.217C>T
- MANE Select
- NM_001366178
- Type
- single nucleotide variant
- Location
- chr19:35778307 (GRCh38)
- Gene constraint
- LOEUF 0.59 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.54
- Residue 73
- the px; atypical domain
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-pro73ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown