Used Design Manager to replace Frame Members instead of using "Edit Definition' on the Frame itself. The name of the Frame Members updated in Pathfinder, but nothing physically changed.
Solution
This happened because Design Manager is only changing the link, and does not load the frame into memory. Because of this the Frame cannot be updated. After performing this action in Design Manager, Edit Definition on the Frame will no longer work. You will have to delete the Frame and recreate it. This is working as designed.
Notes and References
Hardware/Software Configuration
Platform: INTL64
OS: windows
OS Version: 10-20h2
Product: SOLID_EDGE
Application: ASSEMBLY
Version: V222MP6
Function: FRAME
Ref: 001-10367409