MEN1 p.Gln450=
c.1350G>A · rs1592636161 · VCV1059878
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
multiple endocrine neoplasia type 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.91 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.73 | loss · gain 0.28 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 5.9 | GERP 1.5, phastCons 1 |
| Overall | ||
| CADD | 23.4 | 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
- MEN1
- Protein
- p.Gln450=
- Coding
- c.1350G>A
- MANE Select
- NM_001370259
- dbSNP
- rs1592636161
- Type
- single nucleotide variant
- Location
- chr11:64805034 (GRCh38)
- Gene constraint
- LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.13 · 69 PDB
- Residue 450
- an α-helix
Disease context
multiple endocrine neoplasia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Multiple endocrine neoplasia type 1 (Orphanet):
- Inheritance
- Autosomal dominant, Not applicable
- Onset
- All ages
- Prevalence
- 1-9 / 100 000 (Europe)
Similar variants
- MEN1 p.Gln450His Likely pathogenic ★★ ⚠ same residue
- MEN1 p.Gln450Glu Uncertain significance ★★ same residue
- MEN1 p.Gln450Ter Pathogenic ★★ same residue
- MEN1 p.Gln450Arg Uncertain significance ★ ⚠ same residue
- MEN1 c.1049+1G>A Pathogenic ★★ same condition
- MEN1 c.1049+1G>C Pathogenic ★★ same condition
- MEN1 c.1049+2T>C Pathogenic/Likely pathogenic ★★ same condition
- MEN1 c.1350+1G>A Pathogenic ★★ same condition
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/men1-p-gln450 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown