Egyptian military search teams received a distress call from the emergency mechanisms of the missing EgyptAir flight at 4.26am (1226 AEST), almost two hours after it disappeared from radar, the airline says.
Aviation officials say the search is now under way for the debris.
They say the “possibility that the plane crashed has been confirmed” as the plane hasn’t landed in any of the nearby airports.
The officials spoke on condition of anonymity because they were not authorised to speak to the press.
The Airbus 320 disappeared from Egyptian air space at 2.30am on Thursday, about 280km from the Egyptian coastline, according to EgyptAir.
It had been due to land at 3.15am.
The plane was carrying 56 passengers and 10 crew.
Flight MS804 left Charles De Gaulle Airport in Paris at 11.09pm local time on a journey that was expected to last about 3 hours 45 minutes.
But the national carrier tweeted the plane “faded from contact” about 16km into Egyptian airspace.
The last known position of the plane – confirmed by the airline to be an Airbus A320 – was above the Mediterranean Sea.
In March, an EgyptAir plane was hijacked and diverted to Cyprus.
A man who admitted to the hijacking and is described by Cypriot authorities as “psychologically unstable” is in custody in Cyprus.
The incident renewed security concerns months after a Russian passenger plane was blown out of the sky over the Sinai Peninsula.
The Russian plane crashed in Sinai on October 31, killing all 224 people on board. Moscow said it was brought down by an explosive device, and a local branch of the extremist Islamic State group has claimed responsibility for planting it.
In 1999, EgyptAir Flight 1990 crashed into the Atlantic Ocean near the Massachusetts island of Nantucket, killing all 217 people aboard.
US investigators filed a final report that concluded its co-pilot switched off the autopilot and pointed the Boeing 767 downward.
But Egyptian officials rejected the notion of suicide altogether, insisting some mechanical reason caused the crash.
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