Application level General settings are used to set some default options for all new Projects as a starting point. Certain Project specific Current Settings can then be adjusted for the current open Project. These are unavailable if there is no open Project.
From the help:
You can customize the behavior of ArcGIS Pro by setting project and application options.
Project options apply only to the currently open project. If there is no open project, they are not enabled.
Application options apply to all new projects. Also, because they typically affect the application state, they often apply to the currently open project (if there is one) and to existing projects when you reopen them. For example, if you change the selection color for map features in the Selection options, the new selection color is used in new projects, the current project, and existing projects that you reopen.
Some application options prompt you to restart ArcGIS Pro. For example, if you change the application theme from light to dark in the General options, the change takes effect after you restart.
Some application options apply only to new projects. For example, in the General options, if you specify that a particular default geodatabase be used for all projects, this setting applies to new projects, but not to the current project or existing projects.
