Which mutation most likely abolishes protein function?

Which mutation in a protein-coding gene is most likely to completely abolish the protein's function?

1. AA single-nucleotide deletion near the start codon✕
2. BA three-nucleotide deletion near the end of the coding sequence✕
3. CA substitution that creates a synonymous codon✕
4. DA conservative leucine-to-isoleucine substitution in a surface loop✕