Thanks to @MatsLindh who recommended a better solution:

from sqlalchemy import Sequence
seq = Sequence('user_column_seq', optional=True)
class User(db.Model):
    id: Mapped[int] = mapped_column(primary_key=True)
    column: Mapped[int] = mapped_column(nullable=True, unique=True)

user1 = User() # NULL
user2 = User(column=seq.next_value()) # next free value