TCF3 p.Ala412=
c.1236C>T · rs374473648 · VCV1357527
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.125%, eas)
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 -20 | GERP -2.6 |
| Overall | ||
| CADD | 0.063 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.125%
East Asian · 56/44,694 alleles
Filtering AF
0.099%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0896%
Overall
0.00929%
148/1,593,218 alleles · rare
exomes 138/1,440,862 · genomes 10/152,356 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.125% | 798 |
| South Asian | 0.0386% | 2,593 |
| African / African-American | 0.00935% | 10,701 |
| Admixed American | 0.00669% | 14,955 |
| European (non-Finnish) | 0.00374% | 26,743 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 30,967 |
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.Ala412=
- Coding
- c.1236C>T
- MANE Select
- NM_003200
- dbSNP
- rs374473648
- Type
- single nucleotide variant
- Location
- chr19:1619406 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.42 · 5 PDB
- Residue 412
- a UniProt-annotated variant site (in agm8b; decreased protein abundance); the 'leucine-zipper' region
Similar variants
- 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
- TCF3 p.Ala109Ser Uncertain significance ★★ ⚠ same type
- TCF3 p.Ala115Thr 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-ala412 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown