SMAD6 p.Pro110=
c.330G>A · VCV3703498
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.15e-05%)
Conditions
1
aortic valve disease 2
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 -1.1 | GERP -3 |
| Overall | ||
| CADD | 5.303 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.15e-05%
Overall
8.15e-05%
1/1,226,992 alleles · very rare
exomes 1/1,075,738 · genomes 0/151,254 · 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
- SMAD6
- Protein
- p.Pro110=
- Coding
- c.330G>A
- MANE Select
- NM_005585
- Type
- single nucleotide variant
- Location
- chr15:66703588 (GRCh38)
- Gene constraint
- LOEUF 1.996 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.34
- Residue 110
- a UniProt-annotated variant site (in aovd2); a UniProt-annotated variant site (likely risk factor for crs7); a UniProt-annotated variant site (risk factor for radioulnar synostosis and macrocephaly); the 'disordered' region
Similar variants
- SMAD6 p.Pro110Ser Uncertain significance ★★ ⚠ same residue
- SMAD6 p.Pro110Arg Uncertain significance ★ ⚠ same residue
- SMAD6 p.Gln218Ter Pathogenic/Likely pathogenic ★★ same condition
- SMAD6 p.Tyr264Ter Pathogenic/Likely pathogenic ★★ same condition
- SMAD6 c.817+4A>G Uncertain significance ★★ same condition
- SMAD6 p.Ala100Pro Uncertain significance ★★ ⚠ same condition
- SMAD6 p.Ala100Thr Uncertain significance ★★ ⚠ same condition
- SMAD6 p.Ala134Thr Uncertain significance ★★ ⚠ 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/smad6-p-pro110 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown