TOPORS p.Pro23=
c.69C>G · rs201113897 · VCV1600428
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0401%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -8.2 | GERP -4.2 |
| Overall | ||
| CADD | 0.489 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0401%
East Asian · 18/44,868 alleles
Filtering AF
0.0259%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0214%
Overall
0.00167%
27/1,612,982 alleles · ultra-rare
exomes 23/1,460,626 · genomes 4/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0401% | 2,493 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,450 |
| African / African-American | 0.00133% | 75,050 |
| European (non-Finnish) | 0.000593% | 168,546 |
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
- TOPORS
- Protein
- p.Pro23=
- Coding
- c.69C>G
- MANE Select
- NM_005802
- dbSNP
- rs201113897
- Type
- single nucleotide variant
- Location
- chr9:32550903 (GRCh38)
- Gene constraint
- LOEUF 0.418 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.39
- Residue 23
- the 'e3 ubiquitin-protein ligase activity' region; the 'disordered' region
Similar variants
- TOPORS p.Pro23Ser Uncertain significance ★★ ⚠ same residue
- TOPORS p.Pro23Leu Uncertain significance ★ ⚠ same residue
- TOPORS p.Arg847Ter Pathogenic/Likely pathogenic ★★ same type
- TOPORS p.Gln811Ter Likely pathogenic ★★ same type
- TOPORS p.Glu808Ter Pathogenic ★★ same type
- TOPORS c.*300A>G Uncertain significance ★★ same type
- TOPORS p.Ala154Ser Uncertain significance ★★ ⚠ same type
- TOPORS p.Ala190Thr 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/topors-p-pro23 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown