GCK p.Ser109Pro
c.325T>C · VCV4895921
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely benign
0.1564 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/3 damaging
AlphaMissense, REVEL, SaProt
Computational evidence
| Protein change | ||
| AlphaMissense | 0.1564 | likely benign |
|---|---|---|
| REVEL | 0.774 | moderately pathogenic-leaning |
| SaProt | LLR -7.10 | tolerated |
| ⇒ REVEL calls this damaging; AlphaMissense and SaProt do not. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 9.3 | GERP 0.84, phastCons 1 |
| Regional constraint | o/e 0.71 | unconstrained · MANE · 7,224 bp · p 1.1e-11 · regional, not allelic |
| Overall | ||
| CADD | 25.8 | 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
- GCK
- Protein
- p.Ser109Pro
- Coding
- c.325T>C
- MANE Select
- NM_000162
- Type
- single nucleotide variant
- Location
- chr7:44152309 (GRCh38)
- Gene constraint
- LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 93.87 · 35 PDB
- Residue 109
- the hexokinase domain; a β-strand; the 'hexokinase small subdomain' region; a UniProt-annotated variant site (in mody2)
Similar variants
- GCK p.Ser109= Likely benign ★ same residue
- GCK c.1019+1G>A Pathogenic ★★★ same type
- GCK c.1019+1G>T Pathogenic ★★★ same type
- GCK c.1019+2T>G Pathogenic ★★★ same type
- GCK c.1019+5G>A Likely pathogenic ★★★ same type
- GCK c.1020-10C>A Likely pathogenic ★★★ same type
- GCK c.1020-1G>A Pathogenic ★★★ same type
- GCK c.1020-1G>C 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/gck-p-ser109pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown