From what we've seen in FotRSU, just a slight change in some of the game's settings, even just the addition or removal of one vessel in the game, can cause a CTD when using a Save from the previous state of the game. Any little change of that sort may as well be considered a major change, and the Save File shouldn't be used any longer. It'd be nice, and definitely easier, to be able to "test" certain aspects of the game by using a Save point, but Single Missions are the closest we can get, and even then, they oftentimes have to be edited a bit to make certain that the "catalog of assets" is correct. I used to just make a new version of a MIS file and call it say TestMissionA or B or whatever, and then as there'd be 8 different versions of a possible future mod update, I started mixing them up, and loading basically something that was guaranteed to crash the game - quite by accident, of course, but it'd crash nonetheless... very frustrating.
Make certain you're not running into that first. But also suspect a bad case of "mod soup" if a new MIS you create does the same thing...
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