Only one version of a character, gender-swapped or not, time warped or not, will be approved. If John Smith is in play, Jane Smith will not be approved even if she's from another reality. Nor will the John Smith who was transplanted to a different decade or century and given their own comic book.
If a character is from an alternate reality but could be apped in this reality with little or no issues, they should be. (ex: Ultimate Colossus). Characters generally should not be apped as coming from an alternate universe unless:
1) In canon, they originally come from an alternate universe and shifted realities. (ex: Noh-Varr)
2) Their very existence requires circumstances that don't/won't nececcsarily happen here. (ex: Rachel Summers)
Lastly, only canon comic book alternate versions of a character will be approved. If John Smith exists in Earth-616, he can be apped. If there's an Ultimate John Smith, he can be apped. If John Smith has a cartoon version, he won't be approved nor can someone create their own AU version to be apped.