ARHGAP33 p.Arg830Trp
c.2488C>T · VCV3423257
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.022%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.067 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing |
| Constraint at this position | ||
| Conservation | phyloP 3 | GERP 1.8, phastCons 0.38 |
| Regional constraint | o/e 1.01 | unconstrained · MANE · 1,520 bp · p 0.75 · regional, not allelic |
| Overall | ||
| CADD | 21.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.022%
South Asian · 20/90,852 alleles
Filtering AF
0.0145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0121%
Overall
0.00453%
73/1,610,500 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.022% | 4,543 |
| African / African-American | 0.00668% | 14,964 |
| European (non-Finnish) | 0.00407% | 24,569 |
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.Arg830Trp
- Coding
- c.2488C>T
- MANE Select
- NM_001366178
- Type
- single nucleotide variant
- Location
- chr19:35786958 (GRCh38)
- Gene constraint
- LOEUF 0.59 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 54.54
- Residue 830
- the 'disordered' region
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-arg830trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown