Is CDH1 p.Ile248fs (c.742del) pathogenic?

CDH1 p.Ile248fs (c.742del) is classified Pathogenic in CDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-02). Associated with hereditary neoplastic syndrome.

What condition is associated with CDH1 p.Ile248fs (c.742del)?

CDH1 p.Ile248fs (c.742del) is associated with hereditary neoplastic syndrome (ClinVar).

CDH1 p.Ile248fs

c.742del · VCV3829996

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

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 6 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.4	GERP -0.21, phastCons 1

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

Variant & gene context

Gene: CDH1
Protein: p.Ile248fs
Coding: c.742del
MANE Select: NM_004360
Type: Deletion
Location: chr16:68810251 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 248: a β-strand; the cadherin 1 domain

Full CDH1 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

CDH1 p.Ile248Thr Uncertain significance ★★ ⚠ same residue
CDH1 c.1137+1del Pathogenic ★★★ same condition
CDH1 c.1565+1del Likely pathogenic ★★★ same condition
CDH1 c.1711+2_1711+7del Likely pathogenic ★★★ same condition
CDH1 p.Ala546fs Pathogenic ★★★ same condition
CDH1 p.Arg800fs Pathogenic ★★★ same condition
CDH1 p.Asn369fs Pathogenic ★★★ same condition
CDH1 p.Asn481fs 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/cdh1-p-ile248fs (accessed [today's date]).

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