SOST p.Ala59=
c.177G>A · rs201706408 · VCV764169
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0825%, mid)
Conditions
1
sclerosteosis 1
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 -20 | GERP -2 |
| Overall | ||
| CADD | 1.791 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0825%
Middle Eastern · 5/6,062 alleles
Filtering AF
0.0324%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.021%
Overall
0.00836%
135/1,614,170 alleles · ultra-rare
exomes 131/1,461,842 · genomes 4/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0825% | 1,212 |
| South Asian | 0.0263% | 3,795 |
| European (non-Finnish) | 0.00839% | 11,920 |
| African / African-American | 0.00666% | 15,012 |
| Admixed American | 0.00333% | 30,015 |
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
- SOST
- Protein
- p.Ala59=
- Coding
- c.177G>A
- MANE Select
- NM_025237
- dbSNP
- rs201706408
- Type
- single nucleotide variant
- Location
- chr17:43758565 (GRCh38)
- Gene constraint
- LOEUF 1.634 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 70.73 · 3 PDB
- Residue 59
- the 'disordered' region
Similar variants
- SOST p.Gln24Ter Pathogenic ★★ same condition
- SOST c.-10G>A Likely benign ★★ same condition
- SOST c.-21T>G Likely benign ★★ same condition
- SOST c.*1004G>A Benign ★★ same condition
- SOST c.*1391G>C Likely benign ★★ same condition
- SOST c.*1394C>G Benign ★★ same condition
- SOST c.*320C>T Benign ★★ same condition
- SOST c.*866C>T Benign ★★ same condition
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/sost-p-ala59 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown