SMO p.Pro689=
c.2067T>G · rs1457180773 · VCV741461
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0173%, 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 -6.9 | GERP -7.5 |
| Overall | ||
| CADD | 0.122 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0173%
Middle Eastern · 1/5,776 alleles
Filtering AF
0.00623%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00574%
Overall
0.00652%
101/1,550,184 alleles · ultra-rare
exomes 99/1,397,908 · genomes 2/152,276 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0173% | 5,776 |
| Remaining individualsnot grpmax-eligible | 0.00831% | 12,028 |
| European (non-Finnish) | 0.00752% | 13,306 |
| African / African-American | 0.00409% | 24,427 |
| South Asian | 0.00354% | 28,235 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00349% | 28,640 |
| East Asian | 0.00243% | 41,210 |
| Finnishnot grpmax-eligible | 0.00168% | 59,582 |
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.Pro689=
- Coding
- c.2067T>G
- MANE Select
- NM_005631
- dbSNP
- rs1457180773
- Type
- single nucleotide variant
- Location
- chr7:129212154 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.55 · 15 PDB
- Residue 689
- the 'disordered' region
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-pro689 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown