Plasma will sometimes block mouse button inputs in fullscreen games, if the system cursor ends up over the panel. As in most games the cursor is hidden, this is not directly visible; It can only be noticed by moving the mouse toward the direction of the panel, until you estimate it's touching that screen edge.

In my case I have the panel at the bottom of the screen, which is set to auto-hide visibility. I tested by playing Xonotic in fullscreen mode; If I look straight down in-game, the mouse buttons no longer work... due to the cursor touching the panel in the background, which seems to steal their focus.

This seems to be the exact same effect as described in issue #380476 However it's an entirely different cause, so I'm making this its own bug.