Is MEN1 p.Leu27Pro (c.80T>C) pathogenic?

MEN1 p.Leu27Pro (c.80T>C) is classified Uncertain significance in MEN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-10). AlphaMissense: likely pathogenic (0.9918); Absent from gnomAD v4.1; Associated with multiple endocrine neoplasia type 1.

What condition is associated with MEN1 p.Leu27Pro (c.80T>C)?

MEN1 p.Leu27Pro (c.80T>C) is associated with multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.Leu27Pro (c.80T>C) in the general population?

MEN1 p.Leu27Pro (c.80T>C) is absent from gnomAD v4.1 (gnomAD).

How is Multiple endocrine neoplasia type 1 inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about MEN1 p.Leu27Pro (c.80T>C)?

AlphaMissense predicts likely pathogenic (score 0.9918) — an in-silico prediction, not a clinical call.

MEN1 p.Leu27Pro

c.80T>C · VCV3768302

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9918 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,468)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

multiple endocrine neoplasia type 1

Computational evidence

Protein change
AlphaMissense	0.9918	likely pathogenic
REVEL	0.835	moderately pathogenic-leaning
SaProt	LLR -14.79	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.61	unconstrained · MANE · 4,962 bp · p 4.4e-20 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,609,468). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MEN1
Protein: p.Leu27Pro
Coding: c.80T>C
MANE Select: NM_001370259
Type: single nucleotide variant
Location: chr11:64810030 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 27: an α-helix

Full MEN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple endocrine neoplasia type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple endocrine neoplasia type 1 (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

MEN1 p.Leu27Met Uncertain significance ★★ ⚠ same residue
MEN1 p.Leu27Val Uncertain significance ★ ⚠ same residue
MEN1 p.Leu27= Likely benign ★ 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
MEN1 c.1351-2A>C Pathogenic/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-p-leu27pro (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown