Sen. Joe Manchin says George Clooney pulling support for President Biden's reelection bid is a huge deal ... and he's strongly suggesting Clooney could trigger a change.

The Senator from West Virginia was on the Hill Thursday, when a photog asked about George's damning Biden op-ed in The New York Times ... something he says is critical, because of the source.

Manchin, a Democrat, called George's letter "very telling" and "very serious."

The Senator says Clooney is a very trusted friend of many Democratic members of Congress, and they think a lot of him ... so it sounds like his opinion carries weight.

As you know, Clooney says Biden is not the man he used to be even a couple years ago, joining a mounting chorus calling for POTUS to step aside for a different candidate to run against Donald Trump.

Non-celeb Biden donors, like Whitney Tilson, also tell us the cash flow to Biden's reelection bid is slowing -- not because they don't like Biden, but because they don't think he can win in November.

So far, Biden has refused to cave in ... and he does have some notable supporters out there, like California Gov. Gavin Newsom and, at least publicly, most Dems in Congress.

Check out the video ... Manchin indicates change could be coming at the top of the ticket though, possibly very soon.