United Flight 433 left San Francisco at 10:20 a.m. and landed at Rogue Valley International-Medford Airport in Medford shortly before noon, according to FlightAware. The airport's director, Amber Judd, said the plane landed safely without incident and the external panel was discovered missing during a post-flight inspection.
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The airport paused operations to check the runway and airfield for debris, Judd said, and none was found.
Judd said she believed the United ground crew or pilots doing a routine inspection before the next flight were the ones who noticed the missing panel.
The Boeing 737-800 plane had 139 passengers and six crew members onboard.
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United says it will "thoroughly examine the plane and perform repairs and conduct an investigation to know how the damage occurred."
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The Federal Aviation Administration also said it would investigate.
The missing panel was on the underside of the aircraft where the wing meets the body and just next to the landing gear, United said.
The plane made its first flight in April 1998 and was delivered to Continental Airlines in December of that year, according to the FAA. United Airlines has operated it since Nov. 30, 2011. It is a 737-824, part of the 737-800 series that was a precursor to the Max.
Boeing said, also via email, that it would defer comment to United about the carrier's fleet and operations.
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Incidents have plagued United Airlines in the past few weeks, including several involving planes taking off from SFO -- most notably United Flight 35, where a tire fell off a Boeing 777 during takeoff. The plane was diverted to LAX where it landed safely.
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In January a panel that plugged a space left for an extra emergency door blew off a Max 9 jet in midair just minutes after an Alaska Airlines flight took off from Portland, leaving a gaping hole and forcing pilots to make an emergency landing. There were no serious injuries.
"Well, having things fall off jetliners is not our favorite methodology. It is, in any form or fashion, rare and troublesome," said John Nance, ABC News aviation analyst. "Did somebody fail to close something -- which would have been a human factor. Was it fatigue? Or do we have a situation here that somehow had maintenance. Those questions all have to be answered."
Nance also addressed the longevity of United Flight 433's Boeing 737 plane.
"You know, a lot of the questions that I've been asked so many times over the years is how long can a jetliner stay on serving? Indefinitely. We've got B-52s now that are older, literally, than an aircraft commander flying them in the Air Force," he said.
As for the 139 passengers and six crew members on board, they likely weren't at risk.
"I don't think we had any real danger here in the air. We had danger of anybody who something might fall on that came off an aircraft. That's always a big concern. It's a big concern for the FAA as well as all of us," Nance said.
The incident comes on the heels of a handful mishaps with United flights in the last few weeks. But the experts say would-be passengers shouldn't be worried.
"It's not only safe to fly, it's so much safer to fly than it is to even drive to the airport, and that's not just statistically true. That is true," Nance said.
The Associated Press contributed to this article.