TGFB1 p.Pro348=
c.1044G>A · VCV4734600
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.71e-05%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.5 | GERP -4.3 |
| Overall | ||
| CADD | 6.034 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.71e-05%
European (non-Finnish) · 1/1,147,966 alleles
Overall
6.47e-05%
1/1,545,840 alleles · very rare
exomes 1/1,393,836 · genomes 0/152,004 · 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
- TGFB1
- Protein
- p.Pro348=
- Coding
- c.1044G>A
- MANE Select
- NM_000660
- Type
- single nucleotide variant
- Location
- chr19:41331181 (GRCh38)
- Gene constraint
- LOEUF 0.682 · pLI 0.03 (gnomAD)
- Structure
- AlphaFold pLDDT 80.11 · 22 PDB
- Residue 348
- a turn
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-pro348 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown