@@ -558,7 +558,10 @@ pub(crate) fn subs_parameters(
             if let Some(iparam) = tuple_index(parameters.as_slice(), arg) {
                 subst.call((arg_items[iparam].clone(),), vm)?
             } else {
-                subs_tvars(arg.clone(), parameters, &arg_items, vm)?
+                return Err(vm.new_type_error(format!(
+                    "argument {} with __typing_subst__ was not found in __parameters__",
+                    arg.repr(vm)?
+                )));
             }
         } else {
             subs_tvars(arg.clone(), parameters, &arg_items, vm)?
 
@@ -90,3 +90,25 @@ def __module__(self):
 assert ParamSpec("Unbounded").__bound__ is None
 for bound in (None, "int", "not valid Python!", (int, str), object()):
     assert ParamSpec("BoundSpec", bound=bound).__bound__ is bound
+
+
+# GenericAlias rejects parameters added after its parameter tuple was cached.
+from types import GenericAlias
+
+
+class LateParameter:
+    def __repr__(self):
+        return "late_parameter"
+
+
+first = LateParameter()
+first.__typing_subst__ = lambda value: value
+late = LateParameter()
+alias = GenericAlias(dict, (first, late))
+assert alias.__parameters__ == (first,)
+late.__typing_subst__ = lambda value: value
+with assert_raises(TypeError) as caught:
+    alias[0]
+assert str(caught.exception) == (
+    "argument late_parameter with __typing_subst__ was not found in __parameters__"
+)