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Simple:

sage: q = next_prime(2^128)
sage: p = (x1*x2) + (x3*x4)
sage: p(x2=2)
x3*x4 + 2*x1

But note that :

sage: p.subs(x2==2)
x1*x2 + x3*x4

doesn't work.

HTH,