Flake blocking the nomination is a real threat.
However, didn’t the GOP remove conservatives from committee positions under Boehner? The republicans can do the same to Flake and put somebody else in his place if he tries to block it. Can’t they?
If he blocks a nominee on the executive calendar just to force a vote on an unrelated bill, as he threatened to do with judicial nominees before Kennedy retired, then that would seem to be a good reason for the party to remove him from the committee.
Outside the committee, I think he loses any ability to block the nomination. He would need one more Republican and no Democrat defections, but I think Manchin and at least one or two other Democrats will vote to confirm, depending on who the nominee is.