TOP2B p.Leu751=
c.2253A>G · rs79628592 · VCV775852
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 4.28%, afr)
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 0.87 | GERP -3.4, phastCons 1 |
| Overall | ||
| CADD | 7.29 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
4.28%
African / African-American · 3,211/75,010 alleles
Filtering AF
4.16%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 4.11%
Overall
0.236%
3,813/1,613,474 alleles · low-frequency
exomes 1,757/1,461,232 · genomes 2,056/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 4.28% | 23 |
| Admixed American | 0.482% | 207 |
| Remaining individualsnot grpmax-eligible | 0.338% | 296 |
| Middle Eastern | 0.247% | 404 |
| European (non-Finnish) | 0.00695% | 14,386 |
| South Asian | 0.00549% | 18,206 |
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.Leu751=
- Coding
- c.2253A>G
- MANE Select
- NM_001330700
- dbSNP
- rs79628592
- Type
- single nucleotide variant
- Location
- chr3:25624775 (GRCh38)
- Gene constraint
- LOEUF 0.328 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.09 · 21 PDB
- Residue 751
- an α-helix; the topo iia-type catalytic domain
Similar variants
- TOP2B p.Leu751Ile Likely benign ★★ 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-leu751 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown