SMO p.Ala239=
c.717C>T · rs111482521 · VCV774136
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
rare (popmax 0.991%, mid)
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 -15 | GERP -7.5 |
| Overall | ||
| CADD | 0.331 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.991%
Middle Eastern · 60/6,056 alleles
Filtering AF
0.79%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.718%
Overall
0.635%
10,237/1,611,784 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.991% | 101 |
| Ashkenazi Jewishnot grpmax-eligible | 0.886% | 113 |
| European (non-Finnish) | 0.731% | 137 |
| Finnishnot grpmax-eligible | 0.502% | 199 |
| South Asian | 0.489% | 204 |
| Remaining individualsnot grpmax-eligible | 0.47% | 213 |
| Admixed American | 0.258% | 387 |
| African / African-American | 0.111% | 903 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| East Asian | 0.00894% | 11,182 |
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
- SMO
- Protein
- p.Ala239=
- Coding
- c.717C>T
- MANE Select
- NM_005631
- dbSNP
- rs111482521
- Type
- single nucleotide variant
- Location
- chr7:129205382 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.55 · 15 PDB
- Residue 239
- a disulfide bond; an α-helix
Similar variants
- SMO p.Leu412Phe Pathogenic ★★ ⚠ same type
- SMO p.Arg512Cys Uncertain significance ★★ ⚠ same type
- SMO p.Arg709Gln Uncertain significance ★★ ⚠ same type
- SMO p.Asp201Val Uncertain significance ★★ ⚠ same type
- SMO p.Gly598Val Uncertain significance ★★ ⚠ same type
- SMO p.Leu197= Uncertain significance ★★ same type
- SMO p.Val129Ile Uncertain significance ★★ ⚠ same type
- SMO p.Val195Met 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/smo-p-ala239 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown