Is MEN1 p.Ala49fs (c.139_143dup) pathogenic?

MEN1 p.Ala49fs (c.139143dup) is classified Pathogenic in MEN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-24). Absent from gnomAD; Associated with multiple endocrine neoplasia type 1.

What condition is associated with MEN1 p.Ala49fs (c.139_143dup)?

MEN1 p.Ala49fs (c.139_143dup) is associated with multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.Ala49fs (c.139_143dup) in the general population?

MEN1 p.Ala49fs (c.139_143dup) is absent from gnomAD (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.Ala49fs

c.139_143dup · rs2497282682 · VCV2132920

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

multiple endocrine neoplasia type 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.52	GERP -0.95, phastCons 0.046

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ala49fs
Coding: c.139_143dup
MANE Select: NM_001370259
dbSNP: rs2497282682
Type: Duplication
Location: chr11:64809966 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 49: 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.Ala49Thr Uncertain significance ★★ ⚠ same residue
MEN1 p.Ala49Val Uncertain significance ★★ ⚠ same residue
MEN1 p.Ala49Ser Uncertain significance ★ ⚠ same residue
MEN1 p.Ala380fs Pathogenic ★★ same condition
MEN1 p.Ala467fs Pathogenic ★★ same condition
MEN1 p.Arg108fs Pathogenic ★★ same condition
MEN1 p.Asp123fs Pathogenic ★★ same condition
MEN1 p.Asp136fs 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-ala49fs (accessed [today's date]).

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