GCK p.Phe334fs
c.1000_1009del · VCV3638238
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
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 8 of 10 |
| Splicing | ||
| SpliceAI | — | not assessed · substitutions only |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 0.68, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Variant & gene context
- Gene
- GCK
- Protein
- p.Phe334fs
- Coding
- c.1000_1009del
- MANE Select
- NM_000162
- Type
- Deletion
- Location
- chr7:44146473 (GRCh38)
- Gene constraint
- LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 93.87 · 35 PDB
- Residue 334
- the hexokinase domain; a binding site; an α-helix; the 'hexokinase large subdomain' region; a UniProt-annotated variant site (in mody2); a UniProt-annotated variant site (in mody2 and t2d)
Similar variants
- GCK p.Phe334_Val335delinsLeuMet Conflicting classifications of pathogenicity ★ same residue
- GCK c.1254-12_1257del Pathogenic ★★★ same type
- GCK c.1255_1264delTTCAAGGAGC Likely pathogenic ★★★ same type
- GCK c.579+4del Pathogenic ★★★ same type
- GCK p.Ala449fs Pathogenic ★★★ same type
- GCK p.Ala450fs Likely pathogenic ★★★ same type
- GCK p.Ala460fs Likely pathogenic ★★★ same type
- GCK p.Arg447fs 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-phe334fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown