TGFB1 p.Pro314=
c.942C>T · rs759582721 · VCV1648236
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00133%, afr)
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 4.6 | GERP -0.026, phastCons 1 |
| Overall | ||
| CADD | 12.93 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00133%
African / African-American · 1/75,028 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000372%
6/1,614,146 alleles · very rare
exomes 6/1,461,864 · genomes 0/152,282 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00133% | 75,028 |
| European (non-Finnish) | 0.000424% | 236,005 |
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
- TGFB1
- Protein
- p.Pro314=
- Coding
- c.942C>T
- MANE Select
- NM_000660
- dbSNP
- rs759582721
- Type
- single nucleotide variant
- Location
- chr19:41332200 (GRCh38)
- Gene constraint
- LOEUF 0.682 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 80.11 · 22 PDB
Similar variants
- TGFB1 p.Arg218Cys Pathogenic ★★ same type
- TGFB1 p.Arg218His Pathogenic/Likely pathogenic ★★ ⚠ same type
- TGFB1 p.Tyr171Cys Likely pathogenic ★★ same type
- TGFB1 c.1014+5G>A Uncertain significance ★★ same type
- TGFB1 p.Arg152Trp Uncertain significance ★★ ⚠ same type
- TGFB1 p.Arg185Trp Uncertain significance ★★ ⚠ same type
- TGFB1 p.Arg277Cys Uncertain significance ★★ ⚠ same type
- TGFB1 p.Arg385Gly Uncertain significance ★★ same type
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/tgfb1-p-pro314 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown