GCK p.Arg191=
c.571C>A · VCV4761929
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000593%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>C here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.8 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 6.067 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000593%
European (non-Finnish) · 7/1,180,002 alleles
Filtering AF
0.000247%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000159%
Overall
0.000434%
7/1,613,920 alleles · very rare
exomes 7/1,461,634 · genomes 0/152,286 · joint denominator
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.Arg191=
- Coding
- c.571C>A
- MANE Select
- NM_000162
- Type
- single nucleotide variant
- Location
- chr7:44149977 (GRCh38)
- Gene constraint
- LOEUF 0.866 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 93.87 · 35 PDB
- Residue 191
- the hexokinase domain; an α-helix; the 'hexokinase small subdomain' region; a UniProt-annotated variant site (in mody2); a UniProt-annotated variant site (in mody2 and t2d)
Similar variants
- GCK p.Arg191Gln Pathogenic ★★★ same residue
- GCK p.Arg191Trp Pathogenic ★★★ same residue
- GCK p.Arg191Gly Uncertain significance ★ ⚠ same residue
- GCK p.Arg191Leu Uncertain significance ★ ⚠ 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
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-arg191 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown