TGFB2 p.Ile253=
c.759T>C · rs1659956399 · VCV2031095
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000765%, nfe)
Conditions
1
Loeys-Dietz syndrome 4
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · T>A here scores Δ0.33 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 4.3 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 10.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000765%
European (non-Finnish) · 9/1,176,736 alleles
Filtering AF
0.00036%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000261%
Overall
0.000561%
9/1,603,500 alleles · very rare
exomes 8/1,451,372 · genomes 1/152,128 · 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
- TGFB2
- Protein
- p.Ile253=
- Coding
- c.759T>C
- MANE Select
- NM_003238
- dbSNP
- rs1659956399
- Type
- single nucleotide variant
- Location
- chr1:218435974 (GRCh38)
- Gene constraint
- LOEUF 0.463 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 11 PDB
- Residue 253
- a UniProt-annotated variant site (in lds4); a turn
Similar variants
- TGFB2 p.Ile253Thr Uncertain significance ★ same residue
- TGFB2 c.346+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TGFB2 c.346+1G>T Likely pathogenic ★★ same condition
- TGFB2 c.510+1G>A Likely pathogenic ★★ same condition
- TGFB2 c.932+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TGFB2 c.933-1G>A Pathogenic/Likely pathogenic ★★ same condition
- TGFB2 p.Arg131Ter Pathogenic/Likely pathogenic ★★ same condition
- TGFB2 p.Arg299Gln 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/tgfb2-p-ile253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown