Background: Gastric cancer is the leading cause of death in Asia where a small proportion is hereditary. While some causative genes like CDH1 and mismatch repair genes have been well characterized, many remain unidentified. Methods: We performed whole exome sequencing on peripheral blood DNA of gastric cancer patients suspected to have an underlying hereditary predisposition, defined as young onset cancer diagnosed at or below age forty, and/or strong family history of cancers. Potentially causative mutations were identified using ANNOVAR, the CADD algorithm and HGMD database. Sanger sequencing was performed to confirm mutations identified. Results: Twenty subjects (18 Chinese and 2 Malays) were studied. 70% were males. Median age at cancer diagnosis was 36 (range 24-68). 75% had poorly differentiated adenocarcinomas and 50% had signet ring cells. 9 subjects had young onset cancer without family history, 6 had young onset cancer with family history and 5 had gastric cancer after age 40 but had family history of gastric or Lynch syndrome related cancers. Potentially deleterious germline mutations that may cause hereditary gastric cancer were identified in 9/20 (45%) of subjects. Seven subjects carried 8 deleterious mutations in genes known to cause familial gastric cancer, including CDH1 (n = 1: c.1888C > G(L630V)), MLH1 (n = 2: 428T > A(V143D), n = 1: 2101C > A(Q701K)), MSH6 (n = 2: c.4071_4072insGATT, n = 1: 3205G > C(G1069R)) and TP53 (n = 1: 679G > T(G227X)). A probably deleterious mutation was identified in 1 novel gene, ABCA10 (1328_1331del), in 2 patients with young onset gastric cancer without family history; this variant is present in less than 1% of Asians. Five of the 7 distinct deleterious mutations identified were novel. In addition, 6 subjects carried two PLCE-1 variants (T1469I, H1619R), while another 6 subjects carried a MLL3 S3660L variant, all of which have been reported to be possible low-penetrance variants that increase gastric cancer risk by 1.4 and 2.5 fold respectively. Conclusions: In this cohort of Asian gastric cancer patients suspected to have hereditary gastric cancer, potentially causative rare high penetrance and common low penetrance genetic variants were identified.