I have been noticing that in versions 2.8.1 and 2.8.2 there appears to be some instability in the ArcGIS Pro GUI especially if you lock your PC or if Windows automatically locks your PC due to inactivity. Usually, this results in part or all of the GUI of Pro not responding. However, the map, layout, and catalog tabs still have some functionality. We can pan and zoom, but not select new tools or resources within the ribbon interface. Sometimes, if an edit session is being used, edit saving will fail and there have been edits lost recently. This seems to happen most often over lunch breaks or absences of 10-20 minutes or more. Our current workaround is to make sure to save edits more often, close edit sessions before locking the PC, and close Pro when you know you will be away from the PC for an extended time.
I am just checking the community to see if anyone else has noticed issues with Pro GUI/interface similar to this or whether it is unique to me. If anyone else is having similar issues, I will likely submit a ticket with ESRI to document and maybe track the issue.
I am having a similar issue. This was happening last year and this year with all patch updates, with my current install being 2.9.1. I have not noticed any associated activity that leads to it, but in this instance it was georeferencing a raster. My computer does not required being in lock mode. Every button in the GUI acknowledges hover but is unclickable after testing them all. What is different than the first post, is even ones outside of the ribbon in the TOC and catalog pane will not work. Map tabs cannot be selected. As mentioned above, the map in view will still zoom in with the mouse. The only way to leave Pro in this scenario, since the close button is frozen, is to end its process in task manager. This freeze problem occurs much more often than classic crashes that close the program.