TCF3 p.Ser495=
c.1485C>T · rs144425988 · VCV790196
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.193%, 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 -5 | GERP -2.4 |
| Overall | ||
| CADD | 0.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.193%
African / African-American · 144/74,500 alleles
Filtering AF
0.168%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.158%
Overall
0.0149%
235/1,580,520 alleles · rare
exomes 152/1,428,340 · genomes 83/152,180 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.193% | 517 |
| Middle Eastern | 0.0338% | 2,959 |
| Remaining individualsnot grpmax-eligible | 0.0229% | 4,361 |
| Admixed American | 0.0172% | 5,816 |
| European (non-Finnish) | 0.00517% | 19,332 |
| South Asian | 0.00467% | 21,410 |
| 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.Ser495=
- Coding
- c.1485C>T
- MANE Select
- NM_003200
- dbSNP
- rs144425988
- Type
- single nucleotide variant
- Location
- chr19:1615787 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.42 · 5 PDB
- Residue 495
- a UniProt-annotated variant site (in agm8b; decreased protein abundance); the 'disordered' region
Similar variants
- TCF3 p.Ser495Asn 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-ser495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown