Occasionally, the autopilot can not plot a route to a selected destination in known space either despite no systems having been added to the System avoidance list, which can be viewed by selecting "Manage route". In many cases, this is likely the result of a capsule kill that has happened within one or more systems on the route to the destination system, while the option "Avoid Systems where POD killing has recently occurred" has been selected within the autopilot settings. While this will often clear up on its own after some time, deselecting this option will usually allow the autopilot to create a route once again.
The Autopilot will not be able to plot a route to any destination while located in wormhole space.