I get the feeling no one has a clue yet. It is easy to come up with theories... e.g.

Malfunction in plane - transponder turns off - cabin loses pressure (and everyone on plane goes unconscious or similar) - because cockpit is locked crew does not manage to do anything in time - plane keeps on going - fuel runs out.

of course that is probably totally wrong.

One thing though - if it did fly low over land - I would expect at least someone would have used their cell phone - so I would rule out that option.