SKI p.Ala518=
c.1554G>A · rs770050757 · VCV697033
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0195%, eas)
Conditions
2
Shprintzen-Goldberg syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.3 | GERP -1.8, phastCons 1 |
| Overall | ||
| CADD | 6.708 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0195%
East Asian · 8/40,940 alleles
Filtering AF
0.00967%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00704%
Overall
0.000967%
15/1,551,620 alleles · ultra-rare
exomes 14/1,399,468 · genomes 1/152,152 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0195% | 5,117 |
| Middle Eastern | 0.0166% | 6,016 |
| South Asian | 0.00119% | 84,122 |
| European (non-Finnish) | 0.000436% | 229,446 |
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
- SKI
- Protein
- p.Ala518=
- Coding
- c.1554G>A
- MANE Select
- NM_003036
- dbSNP
- rs770050757
- Type
- single nucleotide variant
- Location
- chr1:2304372 (GRCh38)
- Gene constraint
- LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.18 · 4 PDB
- Residue 518
- the 'disordered' region
Similar variants
- SKI p.Ala518Val Likely benign ★★ same residue
- SKI p.Gly116Glu Pathogenic/Likely pathogenic ★★ same condition
- SKI p.Gly117Arg Pathogenic/Likely pathogenic ★★ same condition
- SKI p.Gly117Ser Pathogenic/Likely pathogenic ★★ same condition
- SKI p.Gly34Cys Pathogenic ★★ ⚠ same condition
- SKI p.Gly34Ser Pathogenic/Likely pathogenic ★★ ⚠ same condition
- SKI p.Gly34Val Pathogenic ★★ ⚠ same condition
- SKI p.Leu32Val Pathogenic ★★ ⚠ 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/ski-p-ala518 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown