Is GCK p.Val203= (c.609G>A) pathogenic?

GCK p.Val203= (c.609G>A) is classified Conflicting classifications of pathogenicity in GCK (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-09-11). Ultra-rare (popmax 0.0173%, afr); Associated with maturity-onset diabetes of the young.

What condition is associated with GCK p.Val203= (c.609G>A)?

GCK p.Val203= (c.609G>A) is associated with maturity-onset diabetes of the young, type 2 diabetes mellitus, maturity-onset diabetes of the young type 2 (ClinVar).

How common is GCK p.Val203= (c.609G>A) in the general population?

GCK p.Val203= (c.609G>A) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

How is MODY inherited?

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

GCK p.Val203=

c.609G>A · rs776703291 · VCV712469

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

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 0.48	GERP -2.1, phastCons 1
Overall
CADD	7.596	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% African / African-American · 13/75,048 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00811%

Overall 0.00105% 17/1,614,140 alleles · ultra-rare exomes 15/1,461,832 · genomes 2/152,308 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,773
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0048%	20,836

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.Val203=
Coding: c.609G>A
MANE Select: NM_000162
dbSNP: rs776703291
Type: single nucleotide variant
Location: chr7:44149830 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 35 PDB
Residue 203: the hexokinase domain; a β-strand; the 'hexokinase small subdomain' region; a UniProt-annotated variant site (in mody2); a UniProt-annotated variant site (in mody2 and t2d)

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

Also linked: type 2 diabetes mellitus maturity-onset diabetes of the young type 2 hyperinsulinemic hypoglycemia, familial, 3 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 p.Val203Ala Pathogenic ★★★ ⚠ same residue
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-val203 (accessed [today's date]).

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