TOP1 p.Lys48=
c.144G>A · rs35905808 · VCV708476
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.429%, nfe)
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 2.1 | GERP -0.85, phastCons 1 |
| Overall | ||
| CADD | 7.03 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.429%
European (non-Finnish) · 5,026/1,171,520 alleles
Filtering AF
0.419%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.415%
Overall
0.353%
5,644/1,599,296 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.429% | 233 |
| Ashkenazi Jewishnot grpmax-eligible | 0.348% | 287 |
| Remaining individualsnot grpmax-eligible | 0.288% | 348 |
| Middle Eastern | 0.199% | 504 |
| South Asian | 0.172% | 582 |
| Finnishnot grpmax-eligible | 0.104% | 959 |
| Admixed American | 0.0953% | 1,049 |
| African / African-American | 0.0629% | 1,589 |
| East Asian | 0.00903% | 11,073 |
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
- TOP1
- Protein
- p.Lys48=
- Coding
- c.144G>A
- MANE Select
- NM_003286
- dbSNP
- rs35905808
- Type
- single nucleotide variant
- Location
- chr20:41061479 (GRCh38)
- Gene constraint
- LOEUF 0.122 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.25 · 15 PDB
- Residue 48
- the 'disordered' region
Similar variants
- TOP1 p.Arg140Gln Uncertain significance ★ ⚠ same type
- TOP1 p.Arg34Trp Uncertain significance ★ ⚠ same type
- TOP1 p.Arg95Gln Uncertain significance ★ ⚠ same type
- TOP1 p.Asn178His Uncertain significance ★ ⚠ same type
- TOP1 p.Asn190Asp Uncertain significance ★ ⚠ same type
- TOP1 p.Asn8Ser Uncertain significance ★ ⚠ same type
- TOP1 p.Asp170Gly Uncertain significance ★ ⚠ same type
- TOP1 p.Lys161Arg 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/top1-p-lys48 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown