Is GCK c.488del pathogenic?

GCK c.488del is classified Pathogenic/Likely pathogenic in GCK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-30). Very rare (popmax 8.48e-05%, nfe); Associated with maturity-onset diabetes of the young.

What condition is associated with GCK c.488del?

GCK c.488del is associated with maturity-onset diabetes of the young (ClinVar).

How common is GCK c.488del in the general population?

GCK c.488del is very rare (popmax 8.48e-05%, nfe) (gnomAD).

How is MODY inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

GCK c.488del

rs1246464603 · VCV447407

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

maturity-onset diabetes of the young

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.9	GERP -0.46, phastCons 1
Non-coding constraint	Z 2.44	1 kb window · o/e 0.84 · regional · uncalibrated
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,856 alleles

Overall 0.000657% 1/152,194 alleles · very rare

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: GCK
Coding: c.488del
MANE Select: NM_000162 · reported on NM_033507
dbSNP: rs1246464603
Type: Deletion
Location: chr7:44150063 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 35 PDB

Full GCK gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

maturity-onset diabetes of the young — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For MODY (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

GCK c.1255_1264delTTCAAGGAGC Likely pathogenic ★★★ same condition
GCK c.579+4del Pathogenic ★★★ same condition
GCK p.Arg447fs Pathogenic ★★★ same condition
GCK p.Ile351_Leu352insTer Likely pathogenic ★★★ same condition
GCK p.Phe150del Pathogenic ★★★ same condition
GCK p.Ser383fs Pathogenic ★★★ same condition
GCK p.Arg377_Ala379del Uncertain significance ★★★ same condition
GCK p.Cys213del Uncertain significance ★★★ 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-c-488del (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown