TPI1 p.Phe241=
c.723C>T · rs781975436 · VCV1914973
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0167%, 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 -8.7 | GERP -4.9 |
| Overall | ||
| CADD | 0.87 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0167%
Middle Eastern · 1/5,980 alleles
Filtering AF
0.000803%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00065%
Overall
0.00136%
22/1,613,774 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0167% | 5,980 |
| East Asian | 0.00223% | 44,886 |
| South Asian | 0.0022% | 45,539 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,470 |
| European (non-Finnish) | 0.00136% | 73,744 |
| African / African-American | 0.00134% | 74,906 |
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.Phe241=
- Coding
- c.723C>T
- MANE Select
- NM_000365
- dbSNP
- rs781975436
- Type
- single nucleotide variant
- Location
- chr12:6870356 (GRCh38)
- Gene constraint
- LOEUF 0.563 · pLI 0.87 (gnomAD)
- Structure
- AlphaFold pLDDT 96.87 · 29 PDB
- Residue 241
- a UniProt-annotated variant site (in tpid; hungary; thermolabile); an α-helix
Similar variants
- TPI1 p.Phe241Leu Uncertain significance ★ ⚠ same residue
- TPI1 p.Phe241Ser Pathogenic 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
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-phe241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown