TOP3A p.Glu366=
c.1098A>G · rs1980565781 · VCV2918035
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0117%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.13 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -3.6, phastCons 1 |
| Overall | ||
| CADD | 8.858 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0117%
Admixed American · 7/59,916 alleles
Filtering AF
0.00544%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00381%
Overall
0.000434%
7/1,613,646 alleles · ultra-rare
exomes 5/1,461,480 · genomes 2/152,166 · joint denominator
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.Glu366=
- Coding
- c.1098A>G
- MANE Select
- NM_004618
- dbSNP
- rs1980565781
- Type
- single nucleotide variant
- Location
- chr17:18292828 (GRCh38)
- Gene constraint
- LOEUF 0.737 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 84.14 · 2 PDB
- Residue 366
- the topo ia-type catalytic domain; a UniProt-annotated variant site (in peob5)
Similar variants
- 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
- TOP3A p.Arg341Lys 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-glu366 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown