SKI p.Cys224=
c.672C>T · rs751282340 · VCV2738695
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00167%, amr)
Conditions
2
Shprintzen-Goldberg syndrome
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 4.7 | GERP 2, phastCons 1 |
| Overall | ||
| CADD | 14.01 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00167%
Admixed American · 1/59,960 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.00031%
5/1,612,016 alleles · very rare
exomes 5/1,459,658 · genomes 0/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00167% | 59,960 |
| South Asian | 0.0011% | 91,012 |
| European (non-Finnish) | 0.000254% | 393,239 |
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.Cys224=
- Coding
- c.672C>T
- MANE Select
- NM_003036
- dbSNP
- rs751282340
- Type
- single nucleotide variant
- Location
- chr1:2229438 (GRCh38)
- Gene constraint
- LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.18 · 4 PDB
Similar variants
- 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
- SKI p.Pro35Ser 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-cys224 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown