TCF12 p.Phe221=
c.663C>T · VCV3611159
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.37 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 1.5 | GERP -3, phastCons 1 |
| Overall | ||
| CADD | 12.21 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,976 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000682%
11/1,612,452 alleles · very rare
exomes 11/1,460,242 · genomes 0/152,210 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.004% | 24,992 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,432 |
| European (non-Finnish) | 0.000594% | 168,388 |
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.Phe221=
- Coding
- c.663C>T
- MANE Select
- NM_207037
- Type
- single nucleotide variant
- Location
- chr15:57231235 (GRCh38)
- Gene constraint
- LOEUF 0.609 · pLI 0.02 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 51.13 · 2 PDB
Similar variants
- TCF12 c.1036-1G>T Likely pathogenic ★★ same type
- TCF12 c.1115-2A>G Pathogenic/Likely pathogenic ★★ same type
- TCF12 c.1188+1G>C Pathogenic/Likely pathogenic ★★ same type
- TCF12 c.1188+1G>T Pathogenic/Likely pathogenic ★★ same type
- TCF12 c.686-1G>A Likely pathogenic ★★ same type
- TCF12 p.Arg423Ter Pathogenic/Likely pathogenic ★★ same type
- TCF12 p.Arg485Ter Pathogenic ★★ same type
- TCF12 p.Arg626Ter Pathogenic ★★ 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/tcf12-p-phe221 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown