SKI p.Ser31Trp
c.92C>G · VCV4970895
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.9936 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
2/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.9936 | likely pathogenic · top 10% in SKI |
|---|---|---|
| REVEL | 0.671 | pathogenic-leaning |
| SaProt | LLR -7.85 | tolerated |
| ⇒ AlphaMissense and REVEL call this damaging; SaProt does not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.3 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 1.14 | unconstrained · MANE · 253 bp · p 0.099 · regional, not allelic |
| Overall | ||
| CADD | 26.2 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- SKI
- Protein
- p.Ser31Trp
- Coding
- c.92C>G
- MANE Select
- NM_003036
- Type
- single nucleotide variant
- Location
- chr1:2228858 (GRCh38)
- Gene constraint
- LOEUF 0.809 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 67.18 · 4 PDB
- Residue 31
- a UniProt-annotated variant site (in sgs)
Similar variants
- SKI p.Ser31Pro Pathogenic ★ ⚠ same residue
- SKI p.Ser31= Likely benign ★ same residue
- SKI p.Ser31Ala Likely pathogenic ⚠ same residue
- SKI p.Gly116Glu Pathogenic/Likely pathogenic ★★ same type
- SKI p.Gly117Arg Pathogenic/Likely pathogenic ★★ same type
- SKI p.Gly117Ser Pathogenic/Likely pathogenic ★★ same type
- SKI p.Gly34Cys Pathogenic ★★ ⚠ same type
- SKI p.Gly34Ser Pathogenic/Likely pathogenic ★★ ⚠ 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/ski-p-ser31trp (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown