When creating a new Software Update policy (this could likely happen with an Managed Software Delivery also), and specifying a Computer List as the target you get a generic Management Server error when attempting to edit the target after saving the policy.
"4/17/2015 4:36:20 PM","Failed to open the Resource Target
Object reference not set to an instance of an object."
"4/17/2015 4:36:20 PM","Unhandled exception.
Object reference not set to an instance of an object."
One of the resource GUIDs in the computer list was unable to be found in the CMDB.
Compare the results of a Profiler trace to the number of clients specified in the Computer list in order to determine if the behavior is occurring, for example:
If the Profiler trace stops at the 14th instance of 'spItemExists' when checking the GUIDs against the Symantec_CMDB and there are more than 14 clients specified in the computer list, this indicates that the SMP was unable to find a particular GUID and the process was halted.
To resolve this behavior you will need to determine which machine was the culprit using the Altiris Profiler.