TCF3 p.Ala8=
c.24G>A · rs1337517526 · VCV1895606
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0166%, mid)
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 -2.4 | GERP -3.2 |
| Overall | ||
| CADD | 9.175 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0166%
Middle Eastern · 1/6,022 alleles
Filtering AF
0.00113%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000916%
Overall
0.00159%
25/1,571,134 alleles · ultra-rare
exomes 23/1,418,962 · genomes 2/152,172 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0166% | 6,022 |
| Remaining individualsnot grpmax-eligible | 0.00328% | 30,496 |
| European (non-Finnish) | 0.00172% | 57,975 |
| Finnishnot grpmax-eligible | 0.00169% | 59,170 |
| South Asian | 0.00117% | 85,456 |
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.Ala8=
- Coding
- c.24G>A
- MANE Select
- NM_003200
- dbSNP
- rs1337517526
- Type
- single nucleotide variant
- Location
- chr19:1650225 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.42 · 5 PDB
- Residue 8
- a UniProt-annotated variant site (in a colorectal cancer sample; somatic mutation)
Similar variants
- TCF3 p.Ala8Ser Likely benign ★★ same residue
- TCF3 p.Ala8Val Conflicting classifications of pathogenicity ★ ⚠ 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-ala8 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown