Index: lib/AST/ItaniumMangle.cpp
===================================================================
--- lib/AST/ItaniumMangle.cpp
+++ lib/AST/ItaniumMangle.cpp
@@ -2326,6 +2326,12 @@
     // substitution at the original type.
   }
 
+  // __unaligned is not currently mangled in any way. This implies that it is
+  // not a relevant qualifier for substitutions (while CVR and maybe others
+  // are). This triggers an assertion when this is the only qualifier and the
+  // unqualified type is a class. So let's remove it preventively here.
+  quals.removeUnaligned();
+
   if (quals) {
     mangleQualifiers(quals);
     // Recurse:  even if the qualified type isn't yet substitutable,
Index: test/CodeGenCXX/pr33080.cpp
===================================================================
--- /dev/null
+++ test/CodeGenCXX/pr33080.cpp
@@ -0,0 +1,5 @@
+// RUN: %clang_cc1 -triple %itanium_abi_triple -fms-extensions -emit-llvm -o- %s | FileCheck %s
+
+void f(__unaligned struct A*) {}
+
+// CHECK: define void @_Z1fP1A(%struct.A*)