Is MEN1 p.Leu48= (c.142C>T) pathogenic?

MEN1 p.Leu48= (c.142C>T) is classified Likely benign in MEN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-01). Absent from gnomAD v4.1; Associated with multiple endocrine neoplasia type 1.

What condition is associated with MEN1 p.Leu48= (c.142C>T)?

MEN1 p.Leu48= (c.142C>T) is associated with multiple endocrine neoplasia type 1, hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Leu48= (c.142C>T) in the general population?

MEN1 p.Leu48= (c.142C>T) 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.

MEN1 p.Leu48=

c.142C>T · rs2136192593 · VCV1671905

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

multiple endocrine neoplasia type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP 1.6, phastCons 1
Overall
CADD	12.83	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.Leu48=
Coding: c.142C>T
MANE Select: NM_001370259
dbSNP: rs2136192593
Type: single nucleotide variant
Location: chr11:64809968 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 48: 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

Also linked: hereditary neoplastic syndrome

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.Leu48Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
MEN1 p.Leu48_Ala49insPhePhePhePhePhePheXaaXaaXaaXaaTer Pathogenic ★ same residue
MEN1 p.Leu48fs Pathogenic ★ 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-leu48 (accessed [today's date]).

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