TGFB2 p.Ser288=
c.864C>G · rs373646036 · VCV1597126
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.47e-05%, nfe)
Conditions
1
Loeys-Dietz syndrome 4
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.38 | acceptor loss, 6 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 7.7 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 14.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.47e-05%
European (non-Finnish) · 1/1,179,984 alleles
Overall
6.2e-05%
1/1,614,136 alleles · very rare
exomes 1/1,461,834 · genomes 0/152,302 · 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.Ser288=
- Coding
- c.864C>G
- MANE Select
- NM_003238
- dbSNP
- rs373646036
- Type
- single nucleotide variant
- Location
- chr1:218436079 (GRCh38)
- Gene constraint
- LOEUF 0.463 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 11 PDB
- Residue 288
- a UniProt-annotated variant site (in lds4); an α-helix
Similar variants
- TGFB2 p.Ser288Cys 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-ser288 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown