TCF3 p.Asp533=
c.1599C>T · rs752448046 · VCV1642701
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.103%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.24 | acceptor gain · deltas |
|---|---|---|
| Pangolin | Δ0.28 | gain · loss 0.18 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP -3.9, phastCons 1 |
| Overall | ||
| CADD | 16.18 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.103%
Admixed American · 62/59,988 alleles
Filtering AF
0.0827%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0752%
Overall
0.00572%
92/1,608,444 alleles · rare
exomes 84/1,456,266 · genomes 8/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.103% | 968 |
| East Asian | 0.0245% | 4,080 |
| African / African-American | 0.0107% | 9,366 |
| South Asian | 0.00439% | 22,765 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,434 |
| European (non-Finnish) | 0.000509% | 196,634 |
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.Asp533=
- Coding
- c.1599C>T
- MANE Select
- NM_003200
- dbSNP
- rs752448046
- Type
- single nucleotide variant
- Location
- chr19:1615508 (GRCh38)
- Gene constraint
- LOEUF 1.239 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 52.42 · 5 PDB
- Residue 533
- a UniProt-annotated variant site (in agm8b; decreased protein abundance); the 'disordered' region
Similar variants
- TCF3 p.Glu533Lys Likely benign ★ 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-asp533 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown