TOP2B p.Val153=
c.459A>G · rs60422476 · VCV1164869
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Common
common (popmax 41.5%, afr) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.21 | donor loss, 3 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2 | GERP -2.1, phastCons 1 |
| Overall | ||
| CADD | 10.77 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
41.5%
African / African-American · 29,218/70,360 alleles
Filtering AF
41.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 41%
Overall
28.5%
433,529/1,520,018 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 41.5% | 2 |
| Admixed American | 35% | 3 |
| East Asian | 33% | 3 |
| South Asian | 31.6% | 3 |
| Finnishnot grpmax-eligible | 30% | 3 |
| Amishnot grpmax-eligible | 29.2% | 3 |
| Remaining individualsnot grpmax-eligible | 28.9% | 3 |
| European (non-Finnish) | 27.1% | 4 |
| Ashkenazi Jewishnot grpmax-eligible | 25.3% | 4 |
| Middle Eastern | 22.5% | 4 |
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.Val153=
- Coding
- c.459A>G
- MANE Select
- NM_001330700
- dbSNP
- rs60422476
- Type
- single nucleotide variant
- Location
- chr3:25638247 (GRCh38)
- Gene constraint
- LOEUF 0.328 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.09 · 21 PDB
- Residue 153
- 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-val153 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown