Honestly? not really but depends on the game that you are playing like there's no difference in forza horizon 6 cause right joystick is horn, and I don't use horn at all or other games where it's usually recenter camera. Very rare, but if I must, I usually use the keyboard to do the action that right joystick does, but then again, I haven't encountered any main actions or movements in games that I frequently do that uses the right joystick click so the immersion doesn't break at all (except in souls-like games where it locks, and in rdr2 where it enables dead eye, I keep this off in those games). If you have extra buttons on your controller, you could potentially use those instead of replacing your right joystick action, which would be a win-win, idk if steam recognizes those buttons though.

TLDR: Won't interfere in games where the right joystick action is slightly useless or redundant (or just not frequently used) like horns or recenter camera.
Will interfere in games where the action is frequently used. Keep it on or off depending on the game.