Is CDH1 p.Ile83fs (c.247delinsGTGTGG) pathogenic?

CDH1 p.Ile83fs (c.247delinsGTGTGG) is classified Pathogenic in CDH1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-08). Absent from gnomAD; Associated with hereditary diffuse gastric adenocarcinoma.

What condition is associated with CDH1 p.Ile83fs (c.247delinsGTGTGG)?

CDH1 p.Ile83fs (c.247delinsGTGTGG) is associated with hereditary diffuse gastric adenocarcinoma (ClinVar).

How common is CDH1 p.Ile83fs (c.247delinsGTGTGG) in the general population?

CDH1 p.Ile83fs (c.247delinsGTGTGG) is absent from gnomAD (gnomAD).

How is Hereditary diffuse gastric cancer inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CDH1 p.Ile83fs

c.247delinsGTGTGG · rs2543905020 · VCV2583721

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 diffuse gastric adenocarcinoma

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 3 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.7	GERP -5, phastCons 0.48

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: CDH1
Protein: p.Ile83fs
Coding: c.247delinsGTGTGG
MANE Select: NM_004360
dbSNP: rs2543905020
Type: Indel
Location: chr16:68801753 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB

Full CDH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary diffuse gastric adenocarcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary diffuse gastric cancer (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

CDH1 p.Ile83= Conflicting classifications of pathogenicity ★ same residue
CDH1 p.Ile83Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Pro42fs Pathogenic ★★★ same condition
CDH1 p.Asp514_Thr522delinsValTer Pathogenic/Likely pathogenic ★★ same condition
CDH1 p.Ala137Arg Uncertain significance ★★ same condition
CDH1 p.Asp805Ser Uncertain significance ★★ same condition
CDH1 p.His121_His122delinsGlnAsp Uncertain significance ★★ same condition
CDH1 p.Thr279Asp Uncertain significance ★★ 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-ile83fs (accessed [today's date]).

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