Is MEN1 p.Asp123fs (c.367dup) pathogenic?

MEN1 p.Asp123fs (c.367dup) is classified Pathogenic in MEN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-15). Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Asp123fs (c.367dup)?

MEN1 p.Asp123fs (c.367dup) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 1 (ClinVar).

MEN1 p.Asp123fs

c.367dup · VCV3721985

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

hereditary neoplastic syndrome

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 7.9	GERP 1.6, phastCons 1

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

Variant & gene context

Gene: MEN1
Protein: p.Asp123fs
Coding: c.367dup
MANE Select: NM_001370259
Type: Duplication
Location: chr11:64809742 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 123: an α-helix

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple endocrine neoplasia type 1

Similar variants

MEN1 p.Asp123Asn Uncertain significance ★★ ⚠ same residue
MEN1 p.Asp123= Likely benign ★ same residue
MEN1 p.Ala380fs Pathogenic ★★ same condition
MEN1 p.Ala467fs Pathogenic ★★ same condition
MEN1 p.Ala539fs Pathogenic/Likely pathogenic ★★ same condition
MEN1 p.Arg108fs Pathogenic ★★ same condition
MEN1 p.Asp136fs Pathogenic ★★ same condition
MEN1 p.Asp406fs 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-asp123fs (accessed [today's date]).

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