Is GCK p.Ser100= (c.300C>T) pathogenic?

GCK p.Ser100= (c.300C>T) is classified Likely benign in GCK (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-25). Ultra-rare (popmax 0.0267%, amr); Associated with maturity-onset diabetes of the young.

What condition is associated with GCK p.Ser100= (c.300C>T)?

GCK p.Ser100= (c.300C>T) is associated with maturity-onset diabetes of the young (ClinVar).

How common is GCK p.Ser100= (c.300C>T) in the general population?

GCK p.Ser100= (c.300C>T) is ultra-rare (popmax 0.0267%, amr) (gnomAD).

How is MODY inherited?

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

GCK p.Ser100=

c.300C>T · rs13306389 · VCV1798788

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, amr)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.56	GERP -3.7
Overall
CADD	7.615	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0267% Admixed American · 16/60,012 alleles

Filtering AF 0.0166% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0013% 21/1,614,094 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0267%	3,751
East Asian	0.00223%	44,898
African / African-American	0.00133%	74,924
European (non-Finnish)	0.000254%	393,348

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
Protein: p.Ser100=
Coding: c.300C>T
MANE Select: NM_000162
dbSNP: rs13306389
Type: single nucleotide variant
Location: chr7:44152334 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 35 PDB
Residue 100: the hexokinase domain; a β-strand; the 'hexokinase small subdomain' region; a UniProt-annotated variant site (in mody2)

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.1020-1G>A Pathogenic ★★★ same condition
GCK c.1253+1G>C Pathogenic ★★★ same condition
GCK c.46-2A>G Pathogenic ★★★ same condition
GCK c.580-9T>G Likely pathogenic ★★★ same condition
GCK c.679+1G>A Pathogenic ★★★ same condition
GCK c.679+5G>A Pathogenic ★★★ same condition
GCK c.680-2A>G Pathogenic ★★★ same condition
GCK p.Ala188Thr 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-ser100 (accessed [today's date]).

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