TPI1 p.Pro3=
c.9C>T · rs958568125 · VCV759974
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00178%, 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 -1.8 | GERP -3.6 |
| Overall | ||
| CADD | 10.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00178%
European (non-Finnish) · 21/1,179,682 alleles
Filtering AF
0.00114%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000971%
Overall
0.0013%
21/1,612,532 alleles · very rare
exomes 19/1,460,330 · genomes 2/152,202 · joint denominator
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
- TPI1
- Protein
- p.Pro3=
- Coding
- c.9C>T
- MANE Select
- NM_000365
- dbSNP
- rs958568125
- Type
- single nucleotide variant
- Location
- chr12:6867575 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI 0.87 (gnomAD)
- Structure
- AlphaFold pLDDT 96.87 · 29 PDB
Similar variants
- TPI1 p.Pro3Leu Uncertain significance ★★ ⚠ same residue
- TPI1 p.Glu105Asp Pathogenic/Likely pathogenic ★★ same type
- TPI1 c.543+6C>T Uncertain significance ★★ same type
- TPI1 c.-11G>A Uncertain significance ★★ same type
- TPI1 p.Ala200Val Uncertain significance ★★ ⚠ same type
- TPI1 p.Arg206Cys Uncertain significance ★★ ⚠ same type
- TPI1 p.Arg206His Uncertain significance ★★ ⚠ same type
- TPI1 p.Arg53Trp 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/tpi1-p-pro3 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown