Is MEN1 p.Ile147fs (c.435delinsTT) pathogenic?

MEN1 p.Ile147fs (c.435delinsTT) is classified Pathogenic in MEN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-20). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with MEN1 p.Ile147fs (c.435delinsTT)?

MEN1 p.Ile147fs (c.435delinsTT) is associated with hereditary neoplastic syndrome (ClinVar).

How common is MEN1 p.Ile147fs (c.435delinsTT) in the general population?

MEN1 p.Ile147fs (c.435delinsTT) is absent from gnomAD (gnomAD).

MEN1 p.Ile147fs

c.435delinsTT · rs2497255851 · VCV2626586

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

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 6.6	GERP 0.57, phastCons 1

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.Ile147fs
Coding: c.435delinsTT
MANE Select: NM_001370259
dbSNP: rs2497255851
Type: Indel
Location: chr11:64809675 (GRCh38)
Gene constraint: LOEUF 0.206 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 85.13 · 69 PDB
Residue 147: an α-helix; a UniProt-annotated variant site (in men1)

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

Similar variants

MEN1 p.Ile147Val Uncertain significance ★★ ⚠ same residue
MEN1 p.Ile147= Likely benign ★★ same residue
MEN1 c.825-1_828delinsTACCTAGAGGTT Pathogenic ★ same condition
MEN1 p.Ala464fs Pathogenic ★ same condition
MEN1 p.Arg335fs Pathogenic ★ same condition
MEN1 p.Asp153fs Pathogenic ★ same condition
MEN1 p.Gln64fs Pathogenic ★ same condition
MEN1 p.Gly548fs 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-ile147fs (accessed [today's date]).

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