I am using the steam version.
I am using the real world mod.

I have a SG Williams. I want him to start the game and get most of the minutes. I go to the depth chart and put him playing first in the matrix.
Every game has SG Lostetter starting.

Why?

Go to "GAME OPTIONS" and make sure that "CPU Manage Depth Chart/Sub Matrix" is toggled OFF. If it's toggled ON, then the AI (CPU) will make the decisions regardless of what you've set.

"CPU Manage Depth Chart/Sub Matrix" is gray which I think means toggled off.

Yeah, it turns blue when ON.

So, suggest you ssubmit a Support Ticket along with your game files.