SMO p.Pro684=
c.2052G>A · rs77320475 · VCV1203999
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.44%, nfe)
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 -9.6 | GERP -7.5 |
| Overall | ||
| CADD | 0.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.44%
European (non-Finnish) · 28,101/1,151,568 alleles
Filtering AF
2.42%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.41%
Overall
2%
31,205/1,558,618 alleles · low-frequency
exomes 29,083/1,406,318 · genomes 2,122/152,300 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 2.44% | 41 |
| Remaining individualsnot grpmax-eligible | 1.77% | 57 |
| Finnishnot grpmax-eligible | 1.13% | 88 |
| Admixed American | 0.993% | 101 |
| Amishnot grpmax-eligible | 0.877% | 114 |
| Ashkenazi Jewishnot grpmax-eligible | 0.821% | 122 |
| Middle Eastern | 0.411% | 243 |
| South Asian | 0.395% | 253 |
| African / African-American | 0.325% | 307 |
| East Asian | 0.00966% | 10,351 |
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.Pro684=
- Coding
- c.2052G>A
- MANE Select
- NM_005631
- dbSNP
- rs77320475
- Type
- single nucleotide variant
- Location
- chr7:129212139 (GRCh38)
- Gene constraint
- LOEUF 0.706 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 73.55 · 15 PDB
- Residue 684
- the 'disordered' region
Similar variants
- SMO p.Pro684Leu 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-pro684 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown