TPI1 p.Ser4=
c.12C>T · rs781864765 · VCV742258
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0183%, amr)
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 1.7 | GERP 0.72, phastCons 1 |
| Overall | ||
| CADD | 14.08 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0183%
Admixed American · 11/59,952 alleles
Filtering AF
0.0102%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00786%
Overall
0.000806%
13/1,612,602 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0183% | 5,450 |
| African / African-American | 0.00134% | 74,866 |
| European (non-Finnish) | 8.48e-05% | 1,179,678 |
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.Ser4=
- Coding
- c.12C>T
- MANE Select
- NM_000365
- dbSNP
- rs781864765
- Type
- single nucleotide variant
- Location
- chr12:6867578 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI 0.87 (gnomAD)
- Structure
- AlphaFold pLDDT 96.87 · 29 PDB
- Residue 4
- an α-helix
Similar variants
- 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
- TPI1 p.Asn246Ser 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-ser4 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown