TGFB2 p.Cys413=
c.1239C>T · rs141225367 · VCV213838
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 14 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.13%, afr)
Conditions
2
Cardiovascular phenotype
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 1.8 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 8.819 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.13%
African / African-American · 837/73,944 alleles
Filtering AF
1.07%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.04%
Overall
0.0596%
952/1,597,108 alleles · low-frequency
exomes 465/1,444,872 · genomes 487/152,236 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.13% | 88 |
| Remaining individualsnot grpmax-eligible | 0.0809% | 1,236 |
| Admixed American | 0.0566% | 1,765 |
| Middle Eastern | 0.0501% | 1,995 |
| South Asian | 0.00345% | 29,015 |
| European (non-Finnish) | 0.00238% | 41,989 |
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.Cys413=
- Coding
- c.1239C>T
- MANE Select
- NM_003238
- dbSNP
- rs141225367
- Type
- single nucleotide variant
- Location
- chr1:218441356 (GRCh38)
- Gene constraint
- LOEUF 0.463 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.41 · 11 PDB
- Residue 413
- a disulfide bond; a UniProt-annotated variant site (in lds4); a β-strand
Similar variants
- TGFB2 p.Cys413Arg Uncertain significance ★ ⚠ same residue
- TGFB2 p.Cys413fs Uncertain significance ★★ same residue
- TGFB2 p.Cys413Ter Likely pathogenic ★ 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
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-cys413 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown