Is MEN1 p.Ala467fs (c.1375_1391dup) pathogenic?

MEN1 p.Ala467fs (c.13751391dup) is classified Pathogenic in MEN1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-06-05). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Ala467fs (c.1375_1391dup)?

MEN1 p.Ala467fs (c.1375_1391dup) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 1 (ClinVar).

How common is MEN1 p.Ala467fs (c.1375_1391dup) in the general population?

MEN1 p.Ala467fs (c.1375_1391dup) is absent from gnomAD (gnomAD).

MEN1 p.Ala467fs

c.1375_1391dup · rs2136092832 · VCV1070954

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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	escapes	premature termination codon in the last exon (10 of 10) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -20	GERP -3

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.Ala467fs
Coding: c.1375_1391dup
MANE Select: NM_001370259
dbSNP: rs2136092832
Type: Duplication
Location: chr11:64804775 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 467: the 'disordered' region

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.Ala467Asp Uncertain significance ★★ same residue
MEN1 p.Ala467Val Uncertain significance ★★ same residue
MEN1 p.Ala467= Benign/Likely benign ★★ same residue
MEN1 p.Ala467Ser Uncertain significance ★ ⚠ same residue
MEN1 p.Ala467Thr Conflicting classifications of pathogenicity ★ same residue
MEN1 p.Ala380fs Pathogenic ★★ same condition
MEN1 p.Ala539fs Pathogenic/Likely pathogenic ★★ same condition
MEN1 p.Arg108fs 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-ala467fs (accessed [today's date]).

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