TCF7 p.Pro153His
c.458C>A · rs144072187 · VCV2344726
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0845%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.498 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 4.7 | GERP 0.42, phastCons 1 |
| Regional constraint | o/e 1.21 | unconstrained · MANE · 28 kb · p 5.9e-05 · regional, not allelic |
| Overall | ||
| CADD | 24.7 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0845%
African / African-American · 63/74,548 alleles
Filtering AF
0.0678%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0617%
Overall
0.00804%
129/1,603,640 alleles · ultra-rare
exomes 77/1,451,512 · genomes 52/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0845% | 1,183 |
| Admixed American | 0.0376% | 2,658 |
| Remaining individualsnot grpmax-eligible | 0.00967% | 10,344 |
| South Asian | 0.00558% | 17,911 |
| Finnishnot grpmax-eligible | 0.00313% | 31,933 |
| European (non-Finnish) | 0.00255% | 39,155 |
| East Asian | 0.00226% | 44,342 |
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.Pro153His
- Coding
- c.458C>A
- MANE Select
- NM_003202
- dbSNP
- rs144072187
- Type
- single nucleotide variant
- Location
- chr5:134138075 (GRCh38)
- Gene constraint
- LOEUF 0.624 · pLI 0.15 (gnomAD)
- Structure
- AlphaFold pLDDT 58.11
- Residue 153
- the 'disordered' region
Similar variants
- TCF7 p.Pro153Arg 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
- TCF7 p.Ala74Thr 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-pro153his (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown