TTPA p.Pro8=
c.24C>T · rs140010311 · VCV1562718
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0113%, eas)
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 -5.6 | GERP -3.2 |
| Overall | ||
| CADD | 4.463 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0113%
East Asian · 4/35,502 alleles
Filtering AF
0.00382%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00227%
Overall
0.000605%
9/1,488,476 alleles · ultra-rare
exomes 8/1,336,514 · genomes 1/151,962 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0113% | 8,875 |
| Remaining individualsnot grpmax-eligible | 0.0035% | 28,564 |
| South Asian | 0.00127% | 78,600 |
| European (non-Finnish) | 0.000177% | 563,787 |
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
- TTPA
- Protein
- p.Pro8=
- Coding
- c.24C>T
- MANE Select
- NM_000370
- dbSNP
- rs140010311
- Type
- single nucleotide variant
- Location
- chr8:63085998 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.44 · 6 PDB
- Residue 8
- the 'disordered' region
Similar variants
- TTPA p.Pro8Leu Uncertain significance ★ ⚠ same residue
- TTPA c.205-1G>C Pathogenic ★★ same type
- TTPA c.205-2A>G Pathogenic/Likely pathogenic ★★ same type
- TTPA c.553-1G>T Pathogenic ★★ same type
- TTPA c.663+1G>A Pathogenic/Likely pathogenic ★★ same type
- TTPA p.Ala120Thr Pathogenic/Likely pathogenic ★★ ⚠ same type
- TTPA p.Ala58Asp Likely pathogenic ★★ same type
- TTPA p.Arg134Ter Pathogenic ★★ 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/ttpa-p-pro8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown