If an LWP request gets any of these 500-series codes, $response->is_error will be true, as it will be for any of the 400-series codes. For all other status codes, $response->is_error will be false.
Note that at the time of this writing, the "500 Internal Server Error" code is also used by LWP to signal some error conditions where the remote server can't even be contacted, such as when there's a DNS failure or a TCP/IP connection error.
500 Internal Server Error 501 Not Implemented 502 Bad Gateway 503 Service Unavailable 504 Gateway Timeout 505 HTTP Version Not Supported