TCF12 p.Ser484=
c.1452T>C · rs775754032 · VCV3040515
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000763%, nfe)
Conditions
1
TCF12-related disorder
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 0.93, phastCons 1 |
| Overall | ||
| CADD | 9.152 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000763%
European (non-Finnish) · 9/1,179,976 alleles
Filtering AF
0.000359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00026%
Overall
0.000558%
9/1,614,070 alleles · very rare
exomes 9/1,461,750 · genomes 0/152,320 · joint denominator
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
- TCF12
- Protein
- p.Ser484=
- Coding
- c.1452T>C
- MANE Select
- NM_207037
- dbSNP
- rs775754032
- Type
- single nucleotide variant
- Location
- chr15:57253453 (GRCh38)
- Gene constraint
- LOEUF 0.609 · pLI 0.02 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.13 · 2 PDB
- Residue 484
- the 'disordered' region
Disease context
TCF12-related disorder
Similar variants
- TCF12 c.1036-1G>T Likely pathogenic ★★ same condition
- TCF12 c.1115-2A>G Pathogenic/Likely pathogenic ★★ same condition
- TCF12 c.686-1G>A Likely pathogenic ★★ same condition
- TCF12 p.Arg423Ter Pathogenic/Likely pathogenic ★★ same condition
- TCF12 p.Arg626Ter Pathogenic ★★ same condition
- TCF12 p.Arg90Ter Pathogenic/Likely pathogenic ★★ same condition
- TCF12 p.Ser358Ter Pathogenic ★★ same condition
- TCF12 c.1467+1G>A Pathogenic ★ same condition
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/tcf12-p-ser484 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown