Is GCK p.Val71= (c.213C>T) pathogenic?

GCK p.Val71= (c.213C>T) is classified Conflicting classifications of pathogenicity in GCK (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2026-01-13). Ultra-rare (popmax 0.0448%, nfe); Associated with Transient Neonatal Diabetes, Recessive.

What condition is associated with GCK p.Val71= (c.213C>T)?

GCK p.Val71= (c.213C>T) is associated with Transient Neonatal Diabetes, Recessive, maturity-onset diabetes of the young type 2, hyperinsulinemic hypoglycemia, familial, 3 (ClinVar).

How common is GCK p.Val71= (c.213C>T) in the general population?

GCK p.Val71= (c.213C>T) is ultra-rare (popmax 0.0448%, nfe) (gnomAD).

GCK p.Val71=

c.213C>T · rs143128547 · VCV447393

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0448%, nfe)

Conditions

Transient Neonatal Diabetes, Recessive

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 -3.1	GERP -3.7
Overall
CADD	3.533	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0448% European (non-Finnish) · 529/1,180,024 alleles

Filtering AF 0.0416% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0404%

Overall 0.0342% 552/1,614,156 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0448%	2,231
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Middle Eastern	0.0165%	6,062
South Asian	0.00549%	18,217
Finnishnot grpmax-eligible	0.00312%	32,016
African / African-American	0.00133%	75,026

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.Val71=
Coding: c.213C>T
MANE Select: NM_000162
dbSNP: rs143128547
Type: single nucleotide variant
Location: chr7:44152421 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 35 PDB
Residue 71: the hexokinase domain; 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

Transient Neonatal Diabetes, Recessive

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

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-val71 (accessed [today's date]).

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