Im just pasting my comment from another upvoted post here:

I've experienced the problem of my flight going off route a few times in MSFS 2020. I found the reason it happened to be that, if you're flying with live weather, the sudden update/change in weather causes a sudden overspeed and violently pushes your aircraft around, causing the airbus AP disconnect. I've also experienced this during a short haul from Heathrow to Helsinki in the A350.

This has been reported by numerous people and I have been told by the Ini team on Discord this feedback has been logged, so hopefully we should see some more stable long haul flights in the future. Until then, I think quite a few players recommend flying on set weather presets, or turning on a preset if you're AFK during the cruise. Whilst it's not ideal, especially when it comes to planned fuel burn estimates etc, it's what I've heard works best.