SMO p.Pro753=
c.2259G>A · rs45516102 · VCV778364
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.11%, afr)
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 -5.2 | GERP -7.5 |
| Overall | ||
| CADD | 0.141 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.11%
African / African-American · 830/75,056 alleles
Filtering AF
1.04%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.02%
Overall
0.0605%
977/1,614,098 alleles · low-frequency
exomes 496/1,461,772 · genomes 481/152,326 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.11% | 90 |
| Remaining individualsnot grpmax-eligible | 0.104% | 962 |
| Middle Eastern | 0.099% | 1,010 |
| Admixed American | 0.0666% | 1,501 |
| South Asian | 0.00659% | 15,181 |
| European (non-Finnish) | 0.00246% | 40,690 |
| East Asian | 0.00223% | 44,888 |
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.Pro753=
- Coding
- c.2259G>A
- MANE Select
- NM_005631
- dbSNP
- rs45516102
- Type
- single nucleotide variant
- Location
- chr7:129212346 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.55 · 15 PDB
Similar variants
- SMO p.Pro753Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro753 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown