TGFB2 p.Arg216=
c.648G>A · rs767503001 · VCV1100288
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0467%, amr)
Conditions
2
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 · G>T here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3 | GERP -1, phastCons 1 |
| Overall | ||
| CADD | 8.432 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0467%
Admixed American · 28/59,974 alleles
Filtering AF
0.0332%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0286%
Overall
0.00198%
32/1,613,416 alleles · ultra-rare
exomes 15/1,461,288 · genomes 17/152,128 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0467% | 2,142 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,611 |
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.Arg216=
- Coding
- c.648G>A
- MANE Select
- NM_003238
- dbSNP
- rs767503001
- Type
- single nucleotide variant
- Location
- chr1:218434342 (GRCh38)
- Gene constraint
- LOEUF 0.463 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 11 PDB
- Residue 216
- a UniProt-annotated variant site (in lds4); an α-helix
Similar variants
- 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
- TGFB2 p.Arg299Trp 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-arg216 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown