Is GCK p.Asp113= (c.339C>T) pathogenic?

GCK p.Asp113= (c.339C>T) is classified Benign/Likely benign in GCK (ClinVar, Multiple submitters, 10 submitters; last evaluated 2025-12-16). Low-frequency (popmax 1.47%, afr); Associated with type 2 diabetes mellitus.

What condition is associated with GCK p.Asp113= (c.339C>T)?

GCK p.Asp113= (c.339C>T) is associated with type 2 diabetes mellitus, maturity-onset diabetes of the young type 2, hyperinsulinemic hypoglycemia, familial, 3 (ClinVar).

How common is GCK p.Asp113= (c.339C>T) in the general population?

GCK p.Asp113= (c.339C>T) is low-frequency (popmax 1.47%, afr) (gnomAD).

GCK p.Asp113=

c.339C>T · rs149412035 · VCV36213

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.47%, afr)

Conditions

type 2 diabetes mellitus

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 -5.6	GERP -3.7
Overall
CADD	6.851	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.47% African / African-American · 1,104/75,054 alleles

Filtering AF 1.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.37%

Overall 0.0749% 1,209/1,614,230 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.47%	68
Remaining individualsnot grpmax-eligible	0.0816%	1,226
Admixed American	0.05%	2,001
Middle Eastern	0.033%	3,031
South Asian	0.00329%	30,362
East Asian	0.00223%	44,880
European (non-Finnish)	0.00153%	65,559

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.Asp113=
Coding: c.339C>T
MANE Select: NM_000162
dbSNP: rs149412035
Type: single nucleotide variant
Location: chr7:44152295 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 35 PDB
Residue 113: the hexokinase domain; an α-helix; 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

type 2 diabetes mellitus — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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

Similar variants

GCK c.1019+2T>G Pathogenic ★★★ same condition
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

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-asp113 (accessed [today's date]).

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