The P239S palladin variant has recently been suggested to play a role in hereditary pancreatic cancer. We estimated the contribution of the P239S variant, and surrounding sequence, to familial and early-onset pancreatic cancer. The P239S germline variant was identified in one of 84 high-risk cases and one of 555 controls. The case reported an elderly relative with pancreas cancer. We conclude that this variant does not appear to account for a significant fraction of hereditary or early-onset pancreas cancer.