TOP2A p.Glu571=
c.1713G>A · rs144622532 · VCV783780
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.69%, 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 -0.71 | GERP -1.2, phastCons 0.008 |
| Overall | ||
| CADD | 4.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.69%
African / African-American · 1,265/74,882 alleles
Filtering AF
1.61%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.58%
Overall
0.0906%
1,456/1,606,762 alleles · low-frequency
exomes 692/1,454,564 · genomes 764/152,198 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.69% | 59 |
| Admixed American | 0.16% | 624 |
| Remaining individualsnot grpmax-eligible | 0.103% | 973 |
| Middle Eastern | 0.0496% | 2,018 |
| South Asian | 0.0177% | 5,635 |
| European (non-Finnish) | 0.00119% | 84,000 |
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.Glu571=
- Coding
- c.1713G>A
- MANE Select
- NM_001067
- dbSNP
- rs144622532
- Type
- single nucleotide variant
- Location
- chr17:40406856 (GRCh38)
- Gene constraint
- LOEUF 0.422 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.33 · 15 PDB
- Residue 571
- the toprim domain; a β-strand
Similar variants
- TOP2A p.Pro1194Arg Uncertain significance ★★ ⚠ same type
- TOP2A p.Ala243= Benign ★★ same type
- TOP2A p.Asn774Ile Likely 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-glu571 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown