GCGR p.Pro259=
c.777C>T · rs371527112 · VCV790374
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
rare (popmax 0.434%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -20 | GERP -5.3 |
| Overall | ||
| CADD | 0.104 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.434%
Middle Eastern · 26/5,994 alleles
Filtering AF
0.304%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.261%
Overall
0.0706%
1,086/1,538,026 alleles · rare
exomes 1,011/1,385,678 · genomes 75/152,348 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.434% | 231 |
| Ashkenazi Jewishnot grpmax-eligible | 0.136% | 735 |
| Remaining individualsnot grpmax-eligible | 0.0865% | 1,156 |
| European (non-Finnish) | 0.0803% | 1,245 |
| Admixed American | 0.0392% | 2,552 |
| South Asian | 0.0214% | 4,673 |
| African / African-American | 0.0123% | 8,132 |
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
- GCGR
- Protein
- p.Pro259=
- Coding
- c.777C>T
- MANE Select
- NM_000160
- dbSNP
- rs371527112
- Type
- single nucleotide variant
- Location
- chr17:81811770 (GRCh38)
- Gene constraint
- LOEUF 1.018 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.56 · 28 PDB
Similar variants
- GCGR p.Ala373Thr Uncertain significance ★★ ⚠ same type
- GCGR p.Ala380Thr Uncertain significance ★★ ⚠ same type
- GCGR p.Arg324Cys Uncertain significance ★★ ⚠ same type
- GCGR p.Arg413Gln Uncertain significance ★★ ⚠ same type
- GCGR p.Arg417His Uncertain significance ★★ ⚠ same type
- GCGR p.Leu358Val Uncertain significance ★★ ⚠ same type
- GCGR p.Phe181Ser Uncertain significance ★★ ⚠ same type
- GCGR p.Pro52Thr Uncertain significance ★★ ⚠ 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/gcgr-p-pro259 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown