Exact same error message here.
The problem seems to be related to the digital signature.
When I enable digital signing and try to save the email message I get the same error:
"This message can't be saved to the Drafts mailbox.
The message contains one or more attachments that are too large to be saved in the Drafts mailbox. Try deleting some attachments."
When digital signing is disable everything works as expected.
Console log looks as follows:
default 16:42:52.856985+0100 Mail 0x115f4d150 - [PID=0] WebProcessCache::setApplicationIsActive: (isActive=1)
default 16:42:52.857013+0100 Mail 0x115f298f8 - [PID=0] WebProcessCache::setApplicationIsActive: (isActive=1)
default 16:42:54.039957+0100 Mail <ComposeBackend:0x7fdaaa293a00> Checking compose extensions security status for context <private>.
default 16:42:54.094681+0100 Mail MacOS error: -25300
default 16:42:54.116982+0100 Mail MacOS error: -25300
default 16:42:54.117938+0100 Mail MacOS error: -25300
default 16:42:54.137893+0100 Mail CSSM Exception: -2147416017 CSSMERR_CSP_ACL_ENTRY_TAG_NOT_FOUND
default 16:42:54.150254+0100 Mail CSSM Exception: -2147416017 CSSMERR_CSP_ACL_ENTRY_TAG_NOT_FOUND
default 16:42:54.151796+0100 Mail caught CssmError: -2147416017 CSSMERR_CSP_ACL_ENTRY_TAG_NOT_FOUND
default 16:42:54.152683+0100 Mail CSSM Exception: -2147415780 CSSMERR_CSP_INVALID_KEYATTR_MASK
default 16:42:54.168719+0100 Mail CSSM Exception: -2147416032 CSSMERR_CSP_OPERATION_AUTH_DENIED
default 16:42:54.173746+0100 Mail CSSM Exception: -2147416032 CSSMERR_CSP_OPERATION_AUTH_DENIED
default 16:42:54.175467+0100 Mail Draft save for messageID <D6164E95-6A5D-4D7B-8E4D-B97DF3CC3D03@XXXXXXXXXXXXXXXXXXX.de> failed: error 1
Running latest MacOS 12.2.1