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The most reliable way is to send a letter with a confirmation code (link), which the recipient will have to activate manually.
Less reliable - check through the callout mechanism. However, some systems at the initial stage of the session can give OK for their domains, regardless of the fact that the mailbox exists.
No.
Or more precisely, a refusal is definitely a refusal, but receiving a letter does not mean at all that it has reached the addressee. In corporate networks, very often non-existent mailboxes (fired, etc) are sent to "traps" - no one reads letters that have fallen there.
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