Is GCK p.Arg7fs (c.18del) pathogenic?

GCK p.Arg7fs (c.18del) is classified Pathogenic/Likely pathogenic in GCK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2020-11-19). Absent from gnomAD; Associated with GCK-related disorder.

What condition is associated with GCK p.Arg7fs (c.18del)?

GCK p.Arg7fs (c.18del) is associated with GCK-related disorder (ClinVar).

How common is GCK p.Arg7fs (c.18del) in the general population?

GCK p.Arg7fs (c.18del) is absent from gnomAD (gnomAD).

GCK p.Arg7fs

c.18del · rs2128834774 · VCV1322992

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

GCK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 1 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 0.6, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GCK
Protein: p.Arg7fs
Coding: c.18del
MANE Select: NM_000162
dbSNP: rs2128834774
Type: Deletion
Location: chr7:44188936 (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

GCK-related disorder

Similar variants

GCK p.Asp409fs Pathogenic ★★ same condition
GCK p.Ala208fs Likely pathogenic ★ same condition
GCK p.Asp187fs Likely pathogenic ★ same condition
GCK p.Glu395_Arg403del Likely pathogenic same condition
GCK p.Ser263fs Likely pathogenic same condition
GCK c.208+2T>C Pathogenic/Likely pathogenic ★★ same condition
GCK c.209-1G>A Pathogenic/Likely pathogenic ★★ same condition
GCK p.Arg186Ter 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-arg7fs (accessed [today's date]).

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