In your post it seems that when you say "SMTP validation" you mean connecting to the server and trying a RCPT TO to see if it's accepted. Since you differentiate it from actually sending a confirmation email, I assume you want to do it inline with the user actions. In addition to problems like network issues, DNS failures, etc, gray listing can wreak havoc with this method. Method's vary, but essentially gray listing always defers the first attempt to deliver to recipient per connecting IP. As I said, this can vary, some hosts might reject invalid addresses at first attempt and only defer valid addresses, but there's no reliable way to sort out the different implementations programmatically.

The only way you'll ever be sure that an address is valid and is submitted by its owner who really does want it used for your application is to send a verification email. Well, as long as it doesn't get spam filtered I guess =).