Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_001354803.2:c.382G>A

CA367396913

Gene: GCK (HGNC:2645)

Condition: monogenic diabetes (MONDO:0015967)

Inheritance Mode: Semidominant inheritance

UUID: c55fbd53-753a-4f20-a5f6-37189a97b5c2

Approved on: 2026-04-17

Published on: 2026-04-28

HGVS expressions

NM_001354803.2:c.382G>A

NC_000007.14:g.44145186C>T

CM000669.2:g.44145186C>T

NC_000007.13:g.44184785C>T

CM000669.1:g.44184785C>T

NC_000007.12:g.44151310C>T

NG_008847.1:g.49238G>A

NG_008847.2:g.57985G>A

ENST00000395796.8:c.*1346G>A

ENST00000616242.5:c.*468G>A

ENST00000683378.1:n.574G>A

ENST00000336642.9:c.382G>A

ENST00000345378.7:c.1351G>A

ENST00000403799.8:c.1348G>A

ENST00000671824.1:c.1411G>A

ENST00000672743.1:n.360G>A

ENST00000673284.1:c.1348G>A

ENST00000336642.8:c.400G>A

ENST00000345378.6:c.1351G>A

ENST00000395796.7:c.1345G>A

ENST00000403799.7:c.1348G>A

ENST00000437084.1:c.1297G>A

ENST00000459642.1:n.728G>A

ENST00000616242.4:c.1345G>A

NM_000162.3:c.1348G>A

NM_033507.1:c.1351G>A

NM_033508.1:c.1345G>A

NM_000162.4:c.1348G>A

NM_001354800.1:c.1348G>A

NM_001354801.1:c.337G>A

NM_001354802.1:c.208G>A

NM_001354803.1:c.382G>A

NM_033507.2:c.1351G>A

NM_033508.2:c.1345G>A

NM_000162.5:c.1348G>A

NM_033507.3:c.1351G>A

NM_033508.3:c.1345G>A

Likely Pathogenic

PS4_Moderate PP3 PP2 PM2_Supporting PM5_Supporting

Evidence Links 0

Expert Panel

Monogenic Diabetes VCEP

Criteria Specification Information

Criteria Specification: ClinGen Monogenic Diabetes Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for GCK Version 3.1.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Monogenic Diabetes VCEP

The c.1348G>A variant in the glucokinase gene, GCK, causes an amino acid change of alanine to threonine at codon 450 (p.(Ala450Thr)) of NM_000162.5. GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2). This variant is absent from gnomAD v4.1.0 (PM2_Supporting). This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.909, which is greater than the MDEP VCEP threshold of 0.70 (PP3). This variant was identified in four unrelated indivdiuals with hyperglycemia (PS4_Moderate; PMID: 19790256). Another missense variant at the same residue, c.1348G>T (p.Ala450Ser), has been classified as likely pathogenic by the ClinGen MDEP (PM5_Supporting). In summary, c.1348G>A meets the criteria to be classified as likely pathogenic for monogenic diabetes. ACMG/AMP criteria applied, as specified by the ClinGen MDEP (specification version 3.1.0, approved 10/10/2025): PP2, PP3, PM2_Supporting, PM5_Supporting, PS4_Moderate.

PS4_Moderate

This variant was identified in four unrelated indivdiuals with hyperglycemia (PS4_Moderate; PMID: 19790256).

PP3

This variant is predicted to be deleterious by computational evidence, with a REVEL score of 0.909, which is greater than the MDEP VCEP threshold of 0.70 (PP3).

PP2

GCK is defined by the ClinGen MDEP as a gene that has a low rate of benign missense variation and has pathogenic missense variants as a common mechanism of disease (PP2).

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

PM5_Supporting

Another missense variant at the same residue, c.1348G>T (p.Ala450Ser), has been classified as likely pathogenic by the ClinGen MDEP (PM5_Supporting).

Curation History

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