The pilot reported shortly about the catastrophic engine failure after the takeoff from Montgomery-Gibbs Executive Airport to the east, as per the chief Brian Fennesy at San Diego Fire-Rescue Department.
Nobody was reportedly in the house at the time of the crash.
The pilot and a passenger were taken to a hospital with burns, and two passengers died at the scene, the San Diego Union-Tribune reported. Authorities searched the residence and did not find anyone inside, officials said, and the fire has been put out.
No one on the ground was injured.
The street was lined with more than a dozen fire rigs for several hours.
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Richard King, who lives on the street where the plane crashed, was on his roof putting up Christmas lights when he heard what sounded like a propane tank exploding.
Neighbors tried to get into the house, but said the doors were locked. He told the news outlet that he and others broke the windows of the home and screamed to see if there was anyone inside, but nobody answered.
"All of a sudden, I see a big fire coming toward my house", he said. They didn't hear any cries for help or screaming, he said.
Authorities said at an afternoon press conference two of the four people on board were killed in the crash.