TGFBR1 p.Phe234=
c.702C>T · rs202156059 · VCV919073
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000254%, nfe)
Conditions
2
Loeys-Dietz syndrome
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 0.008 | GERP -5.7, phastCons 0.84 |
| Overall | ||
| CADD | 9.419 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,968 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,614,022 alleles · very rare
exomes 3/1,461,740 · genomes 0/152,282 · 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
- TGFBR1
- Protein
- p.Phe234=
- Coding
- c.702C>T
- MANE Select
- NM_004612
- dbSNP
- rs202156059
- Type
- single nucleotide variant
- Location
- chr9:99137986 (GRCh38)
- Gene constraint
- LOEUF 0.509 · pLI 0.96 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.06 · 45 PDB
- Residue 234
- the protein kinase domain; a β-strand
Similar variants
- TGFBR1 p.Phe234Leu Pathogenic/Likely pathogenic ★★ same residue
- TGFBR1 p.Phe234Cys Uncertain significance ★ ⚠ same residue
- TGFBR1 c.973+1G>A Likely pathogenic ★★ same condition
- TGFBR1 c.974-1G>A Pathogenic ★★ same condition
- TGFBR1 p.Ala355Thr Likely pathogenic ★★ same condition
- TGFBR1 p.Arg225Gly Likely pathogenic ★★ same condition
- TGFBR1 p.Arg487Gln Pathogenic ★★ same condition
- TGFBR1 p.Arg487Trp Pathogenic/Likely 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/tgfbr1-p-phe234 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown