SMAD2 p.Val170=
c.510T>G · VCV4701202
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.015%, amr)
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 0.87 | GERP -4.3, phastCons 0.98 |
| Overall | ||
| CADD | 6.728 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.015%
Admixed American · 9/59,940 alleles
Filtering AF
0.00774%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00579%
Overall
0.00062%
10/1,612,920 alleles · ultra-rare
exomes 2/1,460,798 · genomes 8/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.015% | 6,660 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,434 |
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.Val170=
- Coding
- c.510T>G
- MANE Select
- NM_005901
- Type
- single nucleotide variant
- Location
- chr18:47869253 (GRCh38)
- Gene constraint
- LOEUF 0.249 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.50 · 10 PDB
- Residue 170
- the mh1 domain; a UniProt-annotated variant site (in chtd8)
Similar variants
- SMAD2 p.Val170Phe 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-val170 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown