TGFB3 p.Arg175=
c.525G>C · rs143617644 · VCV1746428
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00935%, afr)
Conditions
2
Rienhoff syndrome
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 -0.16 | GERP -3.6, phastCons 0.23 |
| Overall | ||
| CADD | 13.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00935%
African / African-American · 7/74,898 alleles
Filtering AF
0.00437%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00309%
Overall
0.000434%
7/1,613,980 alleles · very rare
exomes 1/1,461,820 · genomes 6/152,160 · 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
- TGFB3
- Protein
- p.Arg175=
- Coding
- c.525G>C
- MANE Select
- NM_003239
- dbSNP
- rs143617644
- Type
- single nucleotide variant
- Location
- chr14:75971247 (GRCh38)
- Gene constraint
- LOEUF 0.249 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.48 · 11 PDB
Similar variants
- TGFB3 p.Arg175Gln Uncertain significance ★★ ⚠ same residue
- TGFB3 p.Arg175Trp Uncertain significance ★★ ⚠ same residue
- TGFB3 c.517-2A>G Likely pathogenic ★★ same condition
- TGFB3 c.646+1G>C Likely pathogenic ★★ same condition
- TGFB3 c.926+1G>A Likely pathogenic ★★ same condition
- TGFB3 c.927-1G>C Likely pathogenic ★★ same condition
- TGFB3 p.Arg148Ter Pathogenic/Likely pathogenic ★★ same condition
- TGFB3 p.Arg300Gln 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/tgfb3-p-arg175 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown