Accurate interpretation of CDH1 germline variants is critical for physicians and individuals with pathogenic or likely pathogenic variants in CDH1 who are faced with consideration of potentially morbid risk-reduction strategies including total gastrectomy and bilateral mastectomy in females. CDH1-specific variant classification guidelines have been developed by the Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel and recently updated. Here, we demonstrate that the CDH1-specific guidelines reduced the number of variants of uncertain significance submitted to ClinVar and resolved clinically significant conflicts. These guidelines should be utilized to classify germline CDH1 variants to provide the best information to patients and physicians and further support routine updates to gene-specific variant curation guidelines. (By Dr. Xi Luo, https://jmg.bmj.com/content/early/2022/12/06/jmg-2022-108807 )