TOPORS p.Arg628=
c.1884A>G · rs779056957 · VCV1128375
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00667%, 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 -0.84 | GERP -4, phastCons 0.006 |
| Overall | ||
| CADD | 1.919 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00667%
African / African-American · 5/74,918 alleles
Filtering AF
0.00318%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00286%
Overall
0.00335%
54/1,613,946 alleles · very rare
exomes 51/1,461,810 · genomes 3/152,136 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00667% | 14,984 |
| European (non-Finnish) | 0.00415% | 24,082 |
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
- TOPORS
- Protein
- p.Arg628=
- Coding
- c.1884A>G
- MANE Select
- NM_005802
- dbSNP
- rs779056957
- Type
- single nucleotide variant
- Location
- chr9:32542641 (GRCh38)
- Gene constraint
- LOEUF 0.418 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.39
- Residue 628
- the 'disordered' region; the 'interaction with sumo1' region; the 'interaction with top1' region; the 'interaction with p53/tp53' region
Similar variants
- TOPORS p.Arg628Gln Uncertain significance ★★ ⚠ same residue
- TOPORS p.Arg628Ter Pathogenic ★ same residue
- TOPORS p.Arg847Ter Pathogenic/Likely pathogenic ★★ same type
- TOPORS p.Gln811Ter Likely pathogenic ★★ same type
- TOPORS p.Glu808Ter Pathogenic ★★ same type
- TOPORS c.*300A>G Uncertain significance ★★ same type
- TOPORS p.Ala154Ser Uncertain significance ★★ ⚠ same type
- TOPORS p.Ala190Thr 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/topors-p-arg628 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown