TOP2B p.Ser776=
c.2328G>T · rs753548384 · VCV1623758
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.217%, amr)
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 5.3 | GERP 0.96, phastCons 1 |
| Overall | ||
| CADD | 7.286 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.217%
Admixed American · 130/59,972 alleles
Filtering AF
0.186%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.175%
Overall
0.00824%
133/1,613,582 alleles · rare
exomes 123/1,461,470 · genomes 10/152,112 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.217% | 461 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,226 |
| European (non-Finnish) | 8.48e-05% | 1,179,764 |
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
- TOP2B
- Protein
- p.Ser776=
- Coding
- c.2328G>T
- MANE Select
- NM_001330700
- dbSNP
- rs753548384
- Type
- single nucleotide variant
- Location
- chr3:25624700 (GRCh38)
- Gene constraint
- LOEUF 0.328 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.09 · 21 PDB
- Residue 776
- an α-helix; the topo iia-type catalytic domain
Similar variants
- TOP2B p.Ser776Leu Uncertain significance ★ ⚠ same residue
- TOP2B p.Ala1290Thr Uncertain significance ★★ ⚠ same type
- TOP2B p.Ala188Gly Uncertain significance ★★ ⚠ same type
- TOP2B p.Ala777Ser Uncertain significance ★★ ⚠ same type
- TOP2B p.Ala890Ser Uncertain significance ★★ ⚠ same type
- TOP2B p.Arg1047Gln Uncertain significance ★★ ⚠ same type
- TOP2B p.Arg1074Cys Uncertain significance ★★ ⚠ same type
- TOP2B p.Arg1171Gln 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/top2b-p-ser776 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown