Is GCK p.Asp3= (c.9C>T) pathogenic?

GCK p.Asp3= (c.9C>T) is classified Benign/Likely benign in GCK (ClinVar, Multiple submitters, 8 submitters; last evaluated 2025-12-09). Ultra-rare (popmax 0.0767%, amr); Associated with maturity-onset diabetes of the young type 2.

What condition is associated with GCK p.Asp3= (c.9C>T)?

GCK p.Asp3= (c.9C>T) is associated with maturity-onset diabetes of the young type 2, type 2 diabetes mellitus, hyperinsulinemic hypoglycemia, familial, 3 (ClinVar).

How common is GCK p.Asp3= (c.9C>T) in the general population?

GCK p.Asp3= (c.9C>T) is ultra-rare (popmax 0.0767%, amr) (gnomAD).

How is MODY inherited?

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

GCK p.Asp3=

c.9C>T · rs142553382 · VCV389252

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0767%, amr)

Conditions

maturity-onset diabetes of the young type 2

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 1.5	GERP -3.2, phastCons 1
Overall
CADD	11.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0767% Admixed American · 46/59,998 alleles

Filtering AF 0.059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0528%

Overall 0.0121% 196/1,613,938 alleles · ultra-rare exomes 179/1,461,706 · genomes 17/152,232 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0767%	1,304
South Asian	0.0384%	2,601
Middle Eastern	0.033%	3,028
African / African-American	0.00933%	10,716
European (non-Finnish)	0.00856%	11,683
Remaining individualsnot grpmax-eligible	0.0064%	15,626
Finnishnot grpmax-eligible	0.00156%	63,992

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.Asp3=
Coding: c.9C>T
MANE Select: NM_000162
dbSNP: rs142553382
Type: single nucleotide variant
Location: chr7:44188945 (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 type 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: type 2 diabetes mellitus hyperinsulinemic hypoglycemia, familial, 3 maturity-onset diabetes of the young permanent neonatal diabetes mellitus 1

For MODY (Orphanet):

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

Similar variants

GCK c.1020-10C>A Likely pathogenic ★★★ same condition
GCK c.1020-1G>A Pathogenic ★★★ same condition
GCK c.1020-1G>C 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+1G>C 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-asp3 (accessed [today's date]).

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