diff --git a/src/cmd/compile/internal/types2/builtins.go b/src/cmd/compile/internal/types2/builtins.go
index f9db07fdea5d9..4b122bc54077e 100644
--- a/src/cmd/compile/internal/types2/builtins.go
+++ b/src/cmd/compile/internal/types2/builtins.go
@@ -85,7 +85,21 @@ func (check *Checker) builtin(x *operand, call *syntax.CallExpr, id builtinId) (
 		if s, _ := structuralType(S).(*Slice); s != nil {
 			T = s.elem
 		} else {
-			check.errorf(x, invalidArg+"%s is not a slice", x)
+			var cause string
+			switch {
+			case x.isNil():
+				cause = "have untyped nil"
+			case isTypeParam(S):
+				if u := structuralType(S); u != nil {
+					cause = check.sprintf("%s has structural type %s", x, u)
+				} else {
+					cause = check.sprintf("%s has no structural type", x)
+				}
+			default:
+				cause = check.sprintf("have %s", x)
+			}
+			// don't use invalidArg prefix here as it would repeat "argument" in the error message
+			check.errorf(x, "first argument to append must be a slice; %s", cause)
 			return
 		}
 
diff --git a/src/cmd/compile/internal/types2/testdata/check/builtins.src b/src/cmd/compile/internal/types2/testdata/check/builtins.src
index de27f5c632213..358e9c5c0d130 100644
--- a/src/cmd/compile/internal/types2/testdata/check/builtins.src
+++ b/src/cmd/compile/internal/types2/testdata/check/builtins.src
@@ -15,9 +15,9 @@ func append1() {
 	var x int
 	var s []byte
 	_ = append() // ERROR not enough arguments
-	_ = append("foo" /* ERROR not a slice */ )
-	_ = append(nil /* ERROR not a slice */ , s)
-	_ = append(x /* ERROR not a slice */ , s)
+	_ = append("foo" /* ERROR must be a slice */ )
+	_ = append(nil /* ERROR must be a slice */ , s)
+	_ = append(x /* ERROR must be a slice */ , s)
 	_ = append(s)
 	_ = append(s, nil...)
 	append /* ERROR not used */ (s)
@@ -77,7 +77,7 @@ func append3() {
 	_ = append(f2())
 	_ = append(f3())
 	_ = append(f5())
-	_ = append(ff /* ERROR not a slice */ ()) // TODO(gri) better error message
+	_ = append(ff /* ERROR must be a slice */ ()) // TODO(gri) better error message
 }
 
 func cap1() {
diff --git a/src/cmd/compile/internal/types2/testdata/fixedbugs/issue49735.go2 b/src/cmd/compile/internal/types2/testdata/fixedbugs/issue49735.go2
new file mode 100644
index 0000000000000..10e8df2776375
--- /dev/null
+++ b/src/cmd/compile/internal/types2/testdata/fixedbugs/issue49735.go2
@@ -0,0 +1,11 @@
+// Copyright 2022 The Go Authors. All rights reserved.
+// Use of this source code is governed by a BSD-style
+// license that can be found in the LICENSE file.
+
+package p
+
+func _[P1 any, P2 ~byte](s1 P1, s2 P2) {
+        _ = append(nil /* ERROR first argument to append must be a slice; have untyped nil */ , 0)
+        _ = append(s1 /* ERROR s1 .* has no structural type */ , 0)
+        _ = append(s2 /* ERROR s2 .* has structural type byte */ , 0)
+}
diff --git a/src/go/types/builtins.go b/src/go/types/builtins.go
index 8fcfcb935f983..b421b38753e8c 100644
--- a/src/go/types/builtins.go
+++ b/src/go/types/builtins.go
@@ -86,7 +86,21 @@ func (check *Checker) builtin(x *operand, call *ast.CallExpr, id builtinId) (_ b
 		if s, _ := structuralType(S).(*Slice); s != nil {
 			T = s.elem
 		} else {
-			check.invalidArg(x, _InvalidAppend, "%s is not a slice", x)
+			var cause string
+			switch {
+			case x.isNil():
+				cause = "have untyped nil"
+			case isTypeParam(S):
+				if u := structuralType(S); u != nil {
+					cause = check.sprintf("%s has structural type %s", x, u)
+				} else {
+					cause = check.sprintf("%s has no structural type", x)
+				}
+			default:
+				cause = check.sprintf("have %s", x)
+			}
+			// don't use Checker.invalidArg here as it would repeat "argument" in the error message
+			check.errorf(x, _InvalidAppend, "first argument to append must be a slice; %s", cause)
 			return
 		}
 
diff --git a/src/go/types/testdata/check/builtins.src b/src/go/types/testdata/check/builtins.src
index 7fd6a4b03297b..8a4c207a05d66 100644
--- a/src/go/types/testdata/check/builtins.src
+++ b/src/go/types/testdata/check/builtins.src
@@ -15,9 +15,9 @@ func append1() {
 	var x int
 	var s []byte
 	_ = append() // ERROR not enough arguments
-	_ = append("foo" /* ERROR not a slice */ )
-	_ = append(nil /* ERROR not a slice */ , s)
-	_ = append(x /* ERROR not a slice */ , s)
+	_ = append("foo" /* ERROR must be a slice */ )
+	_ = append(nil /* ERROR must be a slice */ , s)
+	_ = append(x /* ERROR must be a slice */ , s)
 	_ = append(s)
 	_ = append(s, nil...)
 	append /* ERROR not used */ (s)
@@ -77,7 +77,7 @@ func append3() {
 	_ = append(f2())
 	_ = append(f3())
 	_ = append(f5())
-	_ = append(ff /* ERROR not a slice */ ()) // TODO(gri) better error message
+	_ = append(ff /* ERROR must be a slice */ ()) // TODO(gri) better error message
 }
 
 func cap1() {
diff --git a/src/go/types/testdata/fixedbugs/issue49735.go2 b/src/go/types/testdata/fixedbugs/issue49735.go2
new file mode 100644
index 0000000000000..10e8df2776375
--- /dev/null
+++ b/src/go/types/testdata/fixedbugs/issue49735.go2
@@ -0,0 +1,11 @@
+// Copyright 2022 The Go Authors. All rights reserved.
+// Use of this source code is governed by a BSD-style
+// license that can be found in the LICENSE file.
+
+package p
+
+func _[P1 any, P2 ~byte](s1 P1, s2 P2) {
+        _ = append(nil /* ERROR first argument to append must be a slice; have untyped nil */ , 0)
+        _ = append(s1 /* ERROR s1 .* has no structural type */ , 0)
+        _ = append(s2 /* ERROR s2 .* has structural type byte */ , 0)
+}