Warning: This article contains spoilers for the Ms. Marvel finale.
Ms. Marvel revealed that Kamala Khan is a mutant, completely jettisoning her comic book origin involving the Inhumans. This same twist occurs often in the comics with other characters, and it also happens in the opposite direction. Numerous characters, including major figures connected to the X-Men in Marvel Comics, turned out not to be mutants after all.
Iconic characters like the Scarlet Witch and Quicksilver saw their origins retconned in the 2010s, a period when the comics began emphasizing the Inhumans over mutants due to movie rights issues. This corporate battle led to many alterations for comic characters, changing them from mutants to in some cases, Inhumans. Comic book readers know mutants factor in another potential game-changing retcon in a current storyline with the potential to alter everything fans know about the X-Men in the comics and live-action.
The X-Men
The biggest retcon involving mutants in Marvel Comics plays out right now in 2022's Judgment Day crossover event, putting the X-Men against the Avengers and Eternals. The comics appear to retcon the X-Men and all mutants as Deviants, the genetic offshoot of Eternals created by the Celestials millions of years in the past.
If this proves true, everything fans believe about mutants changes in an instant. The development presents major ramifications for the X-Men in Marvel Comics and likely alters their inevitable MCU adaptation to build off the characters and backstory established in the Eternals movie.
Toro
Comic book fans know the Human Torch predates the proper Marvel Universe by decades, but they may not be familiar with his Golden Age sidekick Toro. Toro originally gained superpowers from exposure to scientific experiments, but when creators retconned him into Marvel history, he became a mutant.
In a development that echoes Ms. Marvel's MCU experiment in reverse, the comics later revealed Toro wasn't a mutant at all, but in fact an Inhuman. This occurred in All-New Invaders #8 in 2014, the same period Ms. Marvel debuted and other characters saw their origins change to favor the Inhumans.
Deadpool
With his first appearance in The New Mutants #98 and his regenerative healing factor, Deadpool seemingly fit right in with the mutant universe. Later comics revealed he obtained his powers through the Weapon X program which altered many prominent characters like Wolverine, and before then, Wade Wilson was a normal human being.
Deadpool's association with mutants and the X-Men remains strong however both in the comics and in the movies, and likely will when both make their long-awaited debut in the MCU.
Squirrel Girl
Marvel Super-Heroes #8 established Squirrel Girl as a mutant back in the 1990s and she maintained that status for years until The Unbeatable Squirrel Girl # 1 in 2015. That issue, which premiered in the same period that changed Toro's backstory and the general rollback on mutants in favor of the Inhumans, changed Squirrel Girl forever.
The issue makes light of the change by having another character read basically a legal memo saying "Doreen is medically and legally distinct from being a mutant, and I can never take this back."
Multiple Man
Multiple Man features in the best X-Factor comic book issues from the 1990s, but he turned out not to be a mutant. Jamie Madrox's ability to generate exact duplicates of himself played a big role in many comics adventures, as well as the movies, but 2006's X-Factor #11 changed this by revealing he is actually a Changeling.
Changelings differed from mutants in that their powers manifested at birth, unlike most mutants whose abilities tend to emerge in adolescence. Multiple Man remains part of the X-Men universe despite this change.
Franklin Richards
Franklin Richards, the son of Mr. Fantastic and the Invisible Woman, once counted among the most powerful mutants in Marvel Comics. An Omega-Level mutant with the ability to alter reality, he factored heavily into X-Men mythos. That all changed in 2020 when the comics revealed that Franklin had never been a mutant at all.
This shocking development came as Franklin tried to join his fellow mutants on Krakoa. The twist also raises major questions about Franklin's entire comic book history, which seems at odds with the decision.
Quicksilver
Quicksilver once counted among the fastest X-Men in Marvel Comics. The character plays a major role in mutant affairs going back to his first appearance in X-Men #4 in 1964, where he debuted alongside his sister The Scarlet Witch as a member of The Brotherhood of Mutants. In the 2010s, movie rights issues once again appear to have altered his history.
The comics retcon Quicksilver in 2015 to not be a mutant or even Magneto's son, but a product of genetic experimentations performed by The High Evolutionary. This major change in his background remains in place in current comics, despite his movie rights now firmly secured with Marvel Studios.
The Scarlet Witch
The Scarlet Witch's origins changed along with her brother's in 2015. The Scarlet Witch reigned among the most powerful mutants - and the most powerful characters in the Marvel Universe writ large - from her debut in the 1960s. Wanda also played a catastrophic role in erasing most mutants from existence in the seminal House of M storyline.
That act made Wanda a pariah among mutants, perhaps playing into the choice to retcon her years later, but she's since made amends. She recently created a mutant afterlife with her extraordinary power and also reconnected with her found family in Magneto and Polaris.
Honorable Mention: Cloak And Dagger
Cloak and Dagger debuted in Peter Parker, the Spectacular Spider-Man #64 in 1982, where they initially derive their unique powers from synthetic drugs they're forced to take against their will. Marvel Team-Up Annual #6 retconned them to be mutants, with the drugs only serving to activate their mutant genes for the first time. But this changed again.
Though Cloak and Dagger spent some time with the X-Men, Dark X-Men: The Beginning #2 retconned the powerful pair once again, explaining they're not mutants... only for them to be re-retconned as mutants again in a 2018 comic.