TCF3 p.Pro250=
c.750G>A · rs201703361 · VCV717337
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.281%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -2 |
| Overall | ||
| CADD | 0.061 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.281%
European (non-Finnish) · 3,296/1,174,014 alleles
Filtering AF
0.273%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.269%
Overall
0.221%
3,531/1,597,414 alleles · rare
exomes 3,304/1,445,192 · genomes 227/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.281% | 356 |
| Remaining individualsnot grpmax-eligible | 0.15% | 665 |
| Admixed American | 0.121% | 830 |
| Amishnot grpmax-eligible | 0.11% | 910 |
| African / African-American | 0.0521% | 1,918 |
| South Asian | 0.0214% | 4,675 |
| Middle Eastern | 0.0176% | 5,688 |
| Finnishnot grpmax-eligible | 0.015% | 6,647 |
| East Asian | 0.00679% | 14,730 |
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
- TCF3
- Protein
- p.Pro250=
- Coding
- c.750G>A
- MANE Select
- NM_003200
- dbSNP
- rs201703361
- Type
- single nucleotide variant
- Location
- chr19:1622126 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.42 · 5 PDB
- Residue 250
- the 'disordered' region
Similar variants
- TCF3 p.Pro250Leu Uncertain significance ★★ ⚠ same residue
- TCF3 p.Pro250Ser Uncertain significance ★ ⚠ same residue
- TCF3 p.Arg321Ter Pathogenic ★★ same type
- TCF3 p.Glu555Lys Pathogenic ★★ same type
- TCF3 c.1327-3C>A Uncertain significance ★★ same type
- TCF3 c.652+5A>G Uncertain significance ★★ same type
- TCF3 c.955+3A>G Uncertain significance ★★ same type
- TCF3 c.955+6G>A 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/tcf3-p-pro250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown