SMO p.Pro755=
c.2265C>T · rs1284739237 · VCV2657996
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00769%, 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 -0.99 | GERP -1.7 |
| Overall | ||
| CADD | 6.528 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00769%
South Asian · 7/91,084 alleles
Filtering AF
0.00359%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00255%
Overall
0.00105%
17/1,614,132 alleles · very rare
exomes 17/1,461,762 · genomes 0/152,370 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00769% | 13,012 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,254 |
| African / African-American | 0.00133% | 75,072 |
| European (non-Finnish) | 0.000593% | 168,576 |
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.Pro755=
- Coding
- c.2265C>T
- MANE Select
- NM_005631
- dbSNP
- rs1284739237
- Type
- single nucleotide variant
- Location
- chr7:129212352 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.55 · 15 PDB
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-pro755 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown