BACKGROUND: In approximately 10% of all gastric cancer (GC) cases, a heritable cause is suspected. A subset of these cases have a causative germline mutation; however, in most cases the cause remains unknown. Our objective was to assess to what extent these remaining cases may be explained by germline mutations in the novel candidate GC predisposing genes , or . METHODS: We sequenced a large cohort of unexplained young and/or familial patients with GC (n=286) without a germline mutation for germline variants affecting , and using a targeted next-generation sequencing approach based on single-molecule molecular inversion probes. RESULTS: Predicted deleterious germline variants were not encountered in , but recurrently observed in (n=2) and (n=3) in our cohort of patients with GC. In contrast to deleterious variants in , deleterious variants in also occur frequently in the general population. CONCLUSIONS: Based on our results should no longer be considered a GC predisposition gene, whereas deleterious variants are confirmed as an infrequent cause of GC susceptibility. Biallelic germline mutations are at most a very rare cause of GC susceptibility as no additional cases were identified.