TCF3 p.Pro255=
c.765G>A · rs201873505 · VCV777353
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.89%, afr)
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 -10 | GERP -1.8 |
| Overall | ||
| CADD | 0.037 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.89%
African / African-American · 1,416/74,890 alleles
Filtering AF
1.81%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.78%
Overall
0.103%
1,658/1,602,960 alleles · low-frequency
exomes 839/1,450,706 · genomes 819/152,254 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.89% | 53 |
| Admixed American | 0.16% | 627 |
| Remaining individualsnot grpmax-eligible | 0.102% | 984 |
| Middle Eastern | 0.0872% | 1,147 |
| South Asian | 0.0101% | 9,946 |
| European (non-Finnish) | 0.00595% | 16,806 |
| East Asian | 0.00225% | 44,442 |
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.Pro255=
- Coding
- c.765G>A
- MANE Select
- NM_003200
- dbSNP
- rs201873505
- Type
- single nucleotide variant
- Location
- chr19:1622111 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.42 · 5 PDB
- Residue 255
- the 'disordered' region
Similar variants
- TCF3 p.Pro255Leu Uncertain significance ★★ ⚠ same residue
- TCF3 p.Pro255Ser 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-pro255 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown