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Yes, their cosmological structures do not match with each other, and the MCU will never truly cross over with the comic books, no matter how much Marvel Comics' editorial department might want them to for sales reasons.The Sacred Timeline is the MCU Multiverse's version of Earth-616
I think Kevin Fiege said somewhere that the MCU Multiverse is completely separate from the Marvel Comics Multiverse
That said, Marvel Comics has likely created a universe that is similar to the MCU for itself.