I'll risk sounding like Chicken Little here and say that I don't think you can say it's "safe" without further info.
Yeah, I know...if you only knock down the peaks you're left with the same (overall/total) thickness that the valleys had, at least before you take out the sanding marks. But if the orange peel is a matter of texure in the basecoat, that could mean too-thin clear.
The OE finish on some vehicles (e.g., my MPV) have barely enough clear for a few mild corrections...*ever*. Hit that with 2K and by the time you polish out the sanding marks you'd have caused irreperable damage.
OTOH, the finish on other vehicles is so nice and thick that you could level it flat as a mirror and never have a problem. IMO this is one of those "it all depends, how lucky do you feel?" situations.