SKI p.Ala141=
c.423G>C · rs767973122 · VCV2104561
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00195%, nfe)
Conditions
1
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 0.34 | GERP -3.4, phastCons 0.97 |
| Overall | ||
| CADD | 8.592 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00195%
European (non-Finnish) · 23/1,179,176 alleles
Filtering AF
0.0013%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00109%
Overall
0.00143%
23/1,610,898 alleles · very rare
exomes 23/1,458,560 · genomes 0/152,338 · joint denominator
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.Ala141=
- Coding
- c.423G>C
- MANE Select
- NM_003036
- dbSNP
- rs767973122
- Type
- single nucleotide variant
- Location
- chr1:2229189 (GRCh38)
- Gene constraint
- LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.18 · 4 PDB
- Residue 141
- an α-helix
Similar variants
- SKI p.Ala141Thr Uncertain significance ★ ⚠ same residue
- SKI p.Ala141Val Uncertain significance ★ ⚠ same residue
- SKI p.Ala141Ser 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
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-ala141 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown