MINERVA: "If you free her - you'll be destroyed."
JUNO: "It will happen in an instant. There will be no pain."
While it might seem like Minerva is saying that humanity will be destroyed, what she means is that Desmond himself will die in the process of freeing Juno. Which he decides to do. So yeah, Desmond is dead; if there's gonna be another Assassin's Creed game, it will have to be without Desmond. That is, unless they pull some deus ex machina nonsense with Desmond and the animus like how they did with Revelations.