Is GCK p.Asp198= (c.594T>C) pathogenic?

GCK p.Asp198= (c.594T>C) is classified Likely benign in GCK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). Absent from gnomAD v4.1.

How common is GCK p.Asp198= (c.594T>C) in the general population?

GCK p.Asp198= (c.594T>C) is absent from gnomAD v4.1 (gnomAD).

GCK p.Asp198=

c.594T>C · VCV4706608

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -3.9	GERP -3.7
Overall
CADD	1.712	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: GCK
Protein: p.Asp198=
Coding: c.594T>C
MANE Select: NM_000162
Type: single nucleotide variant
Location: chr7:44149845 (GRCh38)
Gene constraint: LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 93.87 · 35 PDB
Residue 198: 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

Similar variants

GCK p.Asp198Val Likely pathogenic ★ same residue
GCK p.Asp198Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
GCK c.1019+1G>A Pathogenic ★★★ same type
GCK c.1019+1G>T Pathogenic ★★★ same type
GCK c.1019+2T>G Pathogenic ★★★ same type
GCK c.1019+5G>A Likely pathogenic ★★★ same type
GCK c.1020-10C>A Likely pathogenic ★★★ same type
GCK c.1020-1G>A Pathogenic ★★★ same type

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-asp198 (accessed [today's date]).

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