TCF7 p.Pro154Arg
c.461C>G · VCV4181561
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00805%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.472 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 3.8 | GERP -2.4, phastCons 0.19 |
| Regional constraint | o/e 1.21 | unconstrained · MANE · 28 kb · p 5.9e-05 · regional, not allelic |
| Overall | ||
| CADD | 20.4 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00805%
African / African-American · 6/74,544 alleles
Filtering AF
0.00349%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00239%
Overall
0.000685%
11/1,606,606 alleles · very rare
exomes 6/1,454,554 · genomes 5/152,052 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00805% | 12,424 |
| South Asian | 0.00222% | 44,970 |
| European (non-Finnish) | 0.000255% | 392,138 |
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.Pro154Arg
- Coding
- c.461C>G
- MANE Select
- NM_003202
- Type
- single nucleotide variant
- Location
- chr5:134138078 (GRCh38)
- Gene constraint
- LOEUF 0.624 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 58.11
- Residue 154
- the 'disordered' region
Similar variants
- 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
- TCF7 p.Ala74Thr Uncertain significance ★ same type
- TCF7 p.Ala78Thr 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-pro154arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown