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It should work with keyboard/gamepad presses but not actually clicking on it, even though all other buttons will work that way in the main menu. I have no clue why it works right out of the box under certain settings and not with others. 

Is there something overtop that could be intercepting the clicks?

There isn't since that screen grabs focus, and the button grabs focus as well. It's something I need to research and dig into since my other game has the reverse issue where clicks are disabled for buttons but there are buttons that still accepts them.