TOPORS p.Ser166=
c.498G>A · rs200690745 · VCV2982900
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
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. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.1 | GERP -4 |
| Overall | ||
| CADD | 5.646 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,880 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000211%
Overall
0.000743%
12/1,614,004 alleles · very rare
exomes 11/1,461,868 · genomes 1/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,880 |
| South Asian | 0.0022% | 45,540 |
| African / African-American | 0.00134% | 74,906 |
| European (non-Finnish) | 0.000678% | 147,502 |
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.Ser166=
- Coding
- c.498G>A
- MANE Select
- NM_005802
- dbSNP
- rs200690745
- Type
- single nucleotide variant
- Location
- chr9:32544027 (GRCh38)
- Gene constraint
- LOEUF 0.418 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.39
- Residue 166
- the 'e3 ubiquitin-protein ligase activity' region; the 'required for dna-binding' region
Similar variants
- 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
- TOPORS p.Ala399Asp Uncertain significance ★★ ⚠ same type
- TOPORS p.Ala56Ser 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-ser166 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown