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What offence is the most grave?

Hare Krsna

Please accept my humble obeisance. All glories to Srila Prabhupada

If one disregards and disrespects Vaishnavas, he commits an offence. Sinful reactions are nullified simply by undergoing ordinary atonement; but offences are not nullified so easily. A sin is committed by both gross and subtle bodies; an offence degrades one's self-realization. Therefore, those who desire to worship the Supreme Lord must be careful not to commit offences.
Srila Bhaktivinod Thakur
As quoted in page 227 of Volume-2 of Srila Bhaktivinoda Vani Vaibhava

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