Re: Not just extensions?
It could as easily be a bug in the page. IIRC, thanks to the magic of threads, the browser can appear responsive while the page is blocked. Or it might have "debounce" logic that has failed. (Something threw and it didn't catch it? Or async code never returned at all?) Or something could have erroneously swallowed the event. Or it could have accidentally set `pointer-events:none`. And so on.
In short there are a myriad things that could go wrong. The first step would be to open the web inspector and see was happening.