GCK p.Val338=
c.1014G>A · rs2484506066 · VCV2632759
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
GCK-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.43 | donor loss, 22 bp away · masked 0 · deltas |
|---|---|---|
| Pangolin | Δ0.62 | loss · gain 0.55 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 1.2 | GERP -0.74, phastCons 1 |
| Overall | ||
| CADD | 16.47 | PHRED · no single calibrated threshold — expert panels disagree |
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.Val338=
- Coding
- c.1014G>A
- MANE Select
- NM_000162
- dbSNP
- rs2484506066
- Type
- single nucleotide variant
- Location
- chr7:44146468 (GRCh38)
- Gene constraint
- LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 93.87 · 35 PDB
- Residue 338
- the hexokinase domain; an α-helix; the 'hexokinase large subdomain' region; a UniProt-annotated variant site (in mody2); a UniProt-annotated variant site (in mody2 and t2d)
Disease context
GCK-related disorder
Similar variants
- GCK p.Val338Gly Uncertain significance ★ ⚠ same residue
- GCK p.Val338Met Uncertain significance ★ same residue
- GCK c.208+2T>C Pathogenic/Likely pathogenic ★★ same condition
- GCK c.209-1G>A Pathogenic/Likely pathogenic ★★ same condition
- GCK p.Arg186Ter Pathogenic ★★ same condition
- GCK p.Arg369Pro Pathogenic/Likely pathogenic ★★ same condition
- GCK p.Asp205His Pathogenic ★★ same condition
- GCK p.Cys129Tyr 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/gck-p-val338 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown