TCF3 p.Ser350=
c.1050G>A · rs367962588 · VCV1603367
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00508%, sas)
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 -3.6 |
| Overall | ||
| CADD | 0.069 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00508%
South Asian · 4/78,744 alleles
Filtering AF
0.00169%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000999%
Overall
0.000987%
15/1,520,320 alleles · very rare
exomes 12/1,368,084 · genomes 3/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00508% | 19,686 |
| Remaining individualsnot grpmax-eligible | 0.00341% | 29,289 |
| Admixed American | 0.00225% | 44,432 |
| European (non-Finnish) | 0.000706% | 141,695 |
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.Ser350=
- Coding
- c.1050G>A
- MANE Select
- NM_003200
- dbSNP
- rs367962588
- Type
- single nucleotide variant
- Location
- chr19:1621011 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.42 · 5 PDB
- Residue 350
- a UniProt-annotated variant site (in agm8b; decreased protein abundance); the 'disordered' region
Similar variants
- TCF3 p.Ser350Leu 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
- TCF3 p.Ala109Ser 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-ser350 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown