TOP3A p.Ser201=
c.603C>T · rs765303480 · VCV932354
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00445%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.51 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.59 | gain · loss 0.57 · SpliceAI calls loss · independent |
| Constraint at this position | ||
| Conservation | phyloP -2.5 | GERP -3.7 |
| Overall | ||
| CADD | 15.6 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00445%
East Asian · 2/44,902 alleles
Filtering AF
0.000738%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000276%
Overall
0.000805%
13/1,614,018 alleles · very rare
exomes 12/1,461,870 · genomes 1/152,148 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00445% | 22,451 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,484 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000763% | 131,114 |
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
- TOP3A
- Protein
- p.Ser201=
- Coding
- c.603C>T
- MANE Select
- NM_004618
- dbSNP
- rs765303480
- Type
- single nucleotide variant
- Location
- chr17:18302620 (GRCh38)
- Gene constraint
- LOEUF 0.737 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.14 · 2 PDB
- Residue 201
- the topo ia-type catalytic domain; a UniProt-annotated variant site (in peob5); an α-helix
Similar variants
- TOP3A p.Ser201fs Uncertain significance ★ same residue
- TOP3A c.990+1G>T Likely pathogenic ★★ same type
- TOP3A p.Arg135Ter Pathogenic/Likely pathogenic ★★ same type
- TOP3A p.Arg177Ter Pathogenic/Likely pathogenic ★★ same type
- TOP3A p.Arg338Ter Pathogenic/Likely pathogenic ★★ same type
- TOP3A p.Ala622Thr Uncertain significance ★★ ⚠ same type
- TOP3A p.Ala642Val Uncertain significance ★★ ⚠ same type
- TOP3A p.Ala941Thr 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/top3a-p-ser201 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown