SMAD2 p.Pro191=
c.573G>A · rs2031719212 · VCV2907941
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 -6 | GERP -4.4 |
| Overall | ||
| CADD | 7.744 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/90,938 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000621%
10/1,609,282 alleles · very rare
exomes 10/1,458,186 · genomes 0/151,096 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,469 |
| African / African-American | 0.00134% | 74,522 |
| European (non-Finnish) | 0.000595% | 168,090 |
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
- SMAD2
- Protein
- p.Pro191=
- Coding
- c.573G>A
- MANE Select
- NM_005901
- dbSNP
- rs2031719212
- Type
- single nucleotide variant
- Location
- chr18:47868405 (GRCh38)
- Gene constraint
- LOEUF 0.249 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50 · 10 PDB
- Residue 191
- a UniProt-annotated variant site (in chtd8)
Similar variants
- SMAD2 p.Pro191Leu Uncertain significance ★★ ⚠ same residue
- SMAD2 c.237-2A>G Likely pathogenic ★★ same type
- SMAD2 p.Arg120Ter Pathogenic/Likely pathogenic ★★ same type
- SMAD2 p.Arg182Ter Pathogenic ★★ same type
- SMAD2 p.Arg321Ter Pathogenic/Likely pathogenic ★★ same type
- SMAD2 p.Gln264Ter Pathogenic/Likely pathogenic ★★ same type
- SMAD2 p.Tyr406Cys Pathogenic/Likely pathogenic ★★ same type
- SMAD2 c.520+4G>A 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/smad2-p-pro191 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown