The crash was reported at about 7:15 p.m. near the 1200 block of Pepper Drive and North Mollison Avenue in the unincorporated Bostonia neighborhood.
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The area is a few miles east of Gillespie Field airport, where the plane was scheduled to land.
Deputies from the San Diego County Sheriff's Department's Santee and Lakeside stations immediately responded to the scene along with the Lakeside Fire Protection District, the California Highway Patrol and the El Cajon Police Department.
"At this time, we do not have information on where the plane was coming from or how many were on board. Firefighters were not able to find any survivors at the crash scene," the sheriff's department said at 11:25 p.m.
News footage from the scene showed the plane's broken wreckage on fire in front of a home.
One home was damaged, but no injuries were reported on the ground, officials said.
The sheriff's department tweeted at 8:57 p.m. that the fire was out, and added that the Federal Aviation Administration and National Transportation Safety Board were notified and will be handling the investigation.
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Anyone who witnessed the crash or has photos or videos from the scene was asked to email witness@ntsb.gov.
Pepper Drive would remain closed between Topper Lane and North Second Street through Wednesday, officials said.
The crash took down an unknown amount of power lines. San Diego Gas & Electric reported that 350 customers in the El Cajon area were without power. Power was expected to be restored by early Tuesday morning, according to the utility.
The American Red Cross would provide assistance Tuesday morning to residents who remain affected by the power outage, according to sheriff's officials.