TTPA p.Pro18=
c.54G>C · rs1227526013 · VCV1093749
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0233%, mid)
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 -15 | GERP -3.6 |
| Overall | ||
| CADD | 0.407 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0233%
Middle Eastern · 1/4,296 alleles
Filtering AF
0.00658%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00467%
Overall
0.00125%
19/1,516,678 alleles · ultra-rare
exomes 15/1,364,656 · genomes 4/152,022 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0233% | 4,296 |
| Admixed American | 0.0142% | 7,046 |
| Remaining individualsnot grpmax-eligible | 0.0017% | 58,666 |
| South Asian | 0.00122% | 82,086 |
| European (non-Finnish) | 0.000789% | 126,770 |
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.Pro18=
- Coding
- c.54G>C
- MANE Select
- NM_000370
- dbSNP
- rs1227526013
- Type
- single nucleotide variant
- Location
- chr8:63085968 (GRCh38)
- Gene constraint
- LOEUF 1.276 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 94.44 · 6 PDB
- Residue 18
- the 'disordered' region
Similar variants
- TTPA p.Pro18Gln Uncertain significance ★ ⚠ same residue
- TTPA p.Pro18Leu 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
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-pro18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown