Is CDH1 p.Arg868fs (c.2602_2612del) pathogenic?

CDH1 p.Arg868fs (c.26022612del) is classified Uncertain significance in CDH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-23). Absent from gnomAD; Associated with hereditary neoplastic syndrome.

What condition is associated with CDH1 p.Arg868fs (c.2602_2612del)?

CDH1 p.Arg868fs (c.2602_2612del) is associated with hereditary neoplastic syndrome, hereditary diffuse gastric adenocarcinoma (ClinVar).

How common is CDH1 p.Arg868fs (c.2602_2612del) in the general population?

CDH1 p.Arg868fs (c.2602_2612del) is absent from gnomAD (gnomAD).

CDH1 p.Arg868fs

c.2602_2612del · rs2152144176 · VCV1511597

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 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 (16 of 16) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.34	GERP -3.7, phastCons 0.29

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.Arg868fs
Coding: c.2602_2612del
MANE Select: NM_004360
dbSNP: rs2152144176
Type: Deletion
Location: chr16:68833452 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB
Residue 868: the 'required for binding alpha, beta and gamma catenins' region

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

Also linked: hereditary diffuse gastric adenocarcinoma

Similar variants

CDH1 p.Arg868Ser Uncertain significance ★★ ⚠ same residue
CDH1 p.Arg868Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Arg868Gly Uncertain significance ★ ⚠ same residue
CDH1 p.Arg868His Conflicting classifications of pathogenicity ★ ⚠ same residue
CDH1 p.Arg868= Benign ★ 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

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-arg868fs (accessed [today's date]).

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