TOP2B p.Asp88=
c.264T>C · rs146891384 · VCV1565114
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.167%, 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 0.72 | GERP -1.9, phastCons 0.94 |
| Overall | ||
| CADD | 7.718 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.167%
African / African-American · 125/75,032 alleles
Filtering AF
0.143%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.134%
Overall
0.00917%
148/1,613,362 alleles · rare
exomes 52/1,461,042 · genomes 96/152,320 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.167% | 600 |
| Admixed American | 0.025% | 4,001 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,490 |
| South Asian | 0.00329% | 30,355 |
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.Asp88=
- Coding
- c.264T>C
- MANE Select
- NM_001330700
- dbSNP
- rs146891384
- Type
- single nucleotide variant
- Location
- chr3:25643761 (GRCh38)
- Gene constraint
- LOEUF 0.328 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.09 · 21 PDB
- Residue 88
- a turn
Similar variants
- 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
- TOP2B p.Arg1305Thr 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-asp88 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown