TCF7 p.Pro134=
c.402C>T · rs372168965 · VCV2655706
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0147%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.16 | GERP 0.2 |
| Overall | ||
| CADD | 8.152 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0147%
African / African-American · 11/74,946 alleles
Filtering AF
0.00815%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00633%
Overall
0.00279%
45/1,613,602 alleles · ultra-rare
exomes 39/1,461,358 · genomes 6/152,244 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0147% | 6,813 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,237 |
| European (non-Finnish) | 0.00271% | 36,875 |
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
- TCF7
- Protein
- p.Pro134=
- Coding
- c.402C>T
- MANE Select
- NM_003202
- dbSNP
- rs372168965
- Type
- single nucleotide variant
- Location
- chr5:134115994 (GRCh38)
- Gene constraint
- LOEUF 0.624 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 58.11
- Residue 134
- the 'disordered' region
Similar variants
- TCF7 p.Pro134Arg Uncertain significance ★ same residue
- TCF7 p.Pro134His Uncertain significance ★ same residue
- TCF7 p.Ala109Ser Uncertain significance ★ same type
- TCF7 p.Ala150Thr Uncertain significance ★ same type
- TCF7 p.Ala364Thr Uncertain significance ★ same type
- TCF7 p.Ala373Thr Uncertain significance ★ same type
- TCF7 p.Ala41Thr Uncertain significance ★ same type
- TCF7 p.Ala42Val 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/tcf7-p-pro134 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown