The Fantastic Four and the X-Men are two of Marvel's most heroic groups. Even as Marvel's mutant heroes have formed their own country and become a world power, they've still done their best to help the humans who once hated and feared them, and despite misgivings about their endgame, Reed Richards, aka Mister Fantastic, ultimately allowed his son Franklin to become part of their endeavor. So, given the altruistic histories of both these groups, not to mention all the times they've worked as allies, why is it starting to seem so likely that Mister Fantastic will be the one to take down Marvel's mutants?
Despite being Marvel's Head of X, Jonathan Hickman's previous Marvel accolades include a long and celebrated run on Fantastic Four, as well as Marvel's Ultimate Comics: The Ultimates, and the path to war between Mister Fantastic and the X-Men relies on elements from all these stories.
Readers of Hickman and R.B. Silva's Powers of X #6 already know that the X-Men's future is looking bleak. Moira MacTaggert's Groundhog Day-style resurrection powers mean that she's seen multiple potential futures, ultimately coming up against the problem of machine life simply out-evolving mutants in the far future - a fact which Charles Xavier's mutant nation has been specifically designed to combat over the long-term. While AI already exists in Marvel canon, and it's already been weaponized against mutants plenty of times, one big clue as to where the mutants' downfall truly begins was given in X-Men #5, when a trio of X-Men were sent to investigate the Vault: a facility which uses accelerated time to rapidly adapt humans and merge them with advanced technology.
If this sounds familiar, it may be because the Vault is similar to the Dome, a facility created by the Reed Richards of the Ultimate Marvel Universe, in which he used accelerated time to create the Children of Tomorrow - an army of cyborg acolytes so powerful they toppled Asgard. Of course, since the events of 2015's Secret Wars, this Reed Richards, now going by the title of the Maker, resides in the mainstream Marvel Universe, making him very much the X-Men's problem, should they draw his ire.
But is that all there is to it - the X-Men are destined to be toppled by an outfit similar to one of Reed's old experiments? Well, not quite, because the X-Men are the aggressors here. In Chip Zdarsky and Terry Dodson's X-Men/Fantastic Four crossover, the X-Men's leader Charles Xavier makes a bold move. Having realized that a device the mainstream, heroic Reed Richards built to help his son can also suppress the mutant gene, Xavier uses the pretense of a friendly visit to wipe the design from Reed's mind and stop him being able to recreate it. Not only that, but he leaves Reed with the knowledge of what he's done.
It's likely that the regular Mister Fantastic understands Charles' reasoning and plans no counter-action, but the same can't be said of the villainous Maker. The Maker is someone who is both capable of inventing the same device - in many ways "he" already thought it up - and who would take huge offense to anyone tampering with his mind. Since the X-Men have proved they'd happily invade his mind, the Maker is left in a situation where his mental autonomy depends on taking down the X-Men - something readers already know has been done successfully with the Maker's favorite tactic.
The evil Reed Richards has every reason to attack the X-Men, and a technique that's already utterly defeated them in one timeline. Even outside the story itself, a war between the X-Men and Reed Richards would reunite the characters of Hickman's prior Marvel triumphs. When the dust of Krakoa's founding settles and the Children of the Vault finally make their move, don't be surprised to see the former Mister Fantastic leading the charge.