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The shooting was reported about 12:40 a.m. in the area of Pier 5, a few blocks from the Ferry Building.
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Officers found a 43-year-old man with a gunshot wound and emergency crews gave him life-saving aid, but he died at the scene, police said.
No arrests have been made and police are asking anyone with information to call the San Francisco Police Department's 24-hour Tip Line at 1-415-575-4444 or Text a Tip to TIP411 and begin the text message with SFPD. Tips may remain anonymous.