TOPORS p.Pro207=
c.621G>A · rs748364310 · VCV1667864
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00659%, sas)
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 -0.088 | GERP -4.3, phastCons 0.85 |
| Overall | ||
| CADD | 9.179 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00659%
South Asian · 6/91,082 alleles
Filtering AF
0.00286%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00195%
Overall
0.00161%
26/1,613,974 alleles · very rare
exomes 26/1,461,712 · genomes 0/152,262 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00659% | 15,180 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,836 |
| Admixed American | 0.00167% | 60,012 |
| African / African-American | 0.00133% | 75,026 |
| European (non-Finnish) | 0.00127% | 78,658 |
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.Pro207=
- Coding
- c.621G>A
- MANE Select
- NM_005802
- dbSNP
- rs748364310
- Type
- single nucleotide variant
- Location
- chr9:32543904 (GRCh38)
- Gene constraint
- LOEUF 0.418 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 49.39
- Residue 207
- the 'required for dna-binding' region
Similar variants
- 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
- TOPORS p.Ala399Asp Uncertain significance ★★ ⚠ same type
- TOPORS p.Ala56Ser 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-pro207 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown