TOP2B p.Gln397=
c.1191G>A · rs371177249 · VCV2971047
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0955%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.65 | acceptor loss, 1 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.44 | GERP 0.39, phastCons 1 |
| Overall | ||
| CADD | 7.235 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0955%
South Asian · 82/85,862 alleles
Filtering AF
0.0787%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0726%
Overall
0.00674%
107/1,587,380 alleles · ultra-rare
exomes 99/1,435,280 · genomes 8/152,100 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0955% | 1,047 |
| Middle Eastern | 0.0542% | 1,845 |
| Remaining individualsnot grpmax-eligible | 0.00489% | 20,469 |
| Admixed American | 0.00188% | 53,208 |
| European (non-Finnish) | 0.00154% | 65,025 |
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.Gln397=
- Coding
- c.1191G>A
- MANE Select
- NM_001330700
- dbSNP
- rs371177249
- Type
- single nucleotide variant
- Location
- chr3:25632521 (GRCh38)
- Gene constraint
- LOEUF 0.328 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 74.09 · 21 PDB
- Residue 397
- a binding site
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-gln397 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown