TOP2A p.Ala243=
c.729A>G · rs34209857 · VCV714733
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.63%, 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 -2.8 | GERP -0.69 |
| Overall | ||
| CADD | 8.235 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.63%
African / African-American · 1,227/75,062 alleles
Filtering AF
1.56%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.53%
Overall
0.105%
1,695/1,614,026 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.63% | 61 |
| Ashkenazi Jewishnot grpmax-eligible | 0.415% | 241 |
| Remaining individualsnot grpmax-eligible | 0.178% | 563 |
| Middle Eastern | 0.148% | 674 |
| Admixed American | 0.148% | 674 |
| South Asian | 0.011% | 9,109 |
| European (non-Finnish) | 0.0107% | 9,364 |
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
- TOP2A
- Protein
- p.Ala243=
- Coding
- c.729A>G
- MANE Select
- NM_001067
- dbSNP
- rs34209857
- Type
- single nucleotide variant
- Location
- chr17:40412819 (GRCh38)
- Gene constraint
- LOEUF 0.422 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.33 · 15 PDB
- Residue 243
- an α-helix
Similar variants
- TOP2A p.Pro1194Arg Uncertain significance ★★ ⚠ same type
- TOP2A p.Asn774Ile Likely benign ★★ same type
- TOP2A p.Glu571= Benign ★★ same type
- TOP2A p.Gly1197Ala Likely benign ★★ same type
- TOP2A p.Gly1197Glu Likely benign ★★ same type
- TOP2A p.Lys976= Benign ★★ same type
- TOP2A p.Pro643= Likely benign ★★ same type
- TOP2A p.Ser390= Benign/Likely benign ★★ 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/top2a-p-ala243 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown