MEN1 c.654+10C>A
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 6.84e-05%)
Conditions
1
multiple endocrine neoplasia type 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| Splice region | donor +10 | near-intronic (+10 nt from the splice site) |
|---|---|---|
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 0.4 | GERP -2.9 |
| Non-coding constraint | Z 4.86 | 1 kb window · o/e 0.68 · regional · uncalibrated |
| Overall | ||
| CADD | 2.313 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.84e-05%
Overall
6.84e-05%
1/1,461,680 alleles · very rare
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
- MEN1
- Coding
- c.654+10C>A
- MANE Select
- NM_001370259
- dbSNP
- rs921850475
- Type
- single nucleotide variant
- Location
- chr11:64807881 (GRCh38)
- Gene constraint
- LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 85.13 · 69 PDB
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 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
- MEN1 c.1351-2A>C Pathogenic/Likely pathogenic ★★ same condition
- MEN1 c.1351-2A>G Pathogenic ★★ same condition
- MEN1 c.1351-9C>G Pathogenic/Likely pathogenic ★★ same condition
- MEN1 c.445+1G>T Likely 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-c-654-plus-10c-a (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown