GCGR p.Phe365=
c.1095C>T · rs5384 · VCV1652397
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Common
common (popmax 21.3%, amr) — too common for a highly-penetrant pathogenic allele
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 -3.4 | GERP -5.3 |
| Overall | ||
| CADD | 4.779 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
21.3%
Admixed American · 10,881/51,000 alleles
Filtering AF
21%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 20.9%
Overall
16.7%
256,645/1,535,976 alleles · common
exomes 233,821/1,383,776 · genomes 22,824/152,200 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 21.3% | 5 |
| East Asian | 20.2% | 5 |
| Amishnot grpmax-eligible | 19.3% | 5 |
| European (non-Finnish) | 17.8% | 6 |
| Finnishnot grpmax-eligible | 15.8% | 6 |
| Remaining individualsnot grpmax-eligible | 15.3% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 11% | 9 |
| Middle Eastern | 10.8% | 9 |
| African / African-American | 9.71% | 10 |
| South Asian | 7.69% | 13 |
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.Phe365=
- Coding
- c.1095C>T
- MANE Select
- NM_000160
- dbSNP
- rs5384
- Type
- single nucleotide variant
- Location
- chr17:81812864 (GRCh38)
- Gene constraint
- LOEUF 1.018 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.56 · 28 PDB
- Residue 365
- an α-helix
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-phe365 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown