Short answer: The mutation most likely to be most dangerous to a cell is a frameshift mutation caused by deletion or insertion of a nucleotide that shifts the reading frame, because it alters downstream amino acid sequence and often introduces premature stop codons, disrupting multiple essential proteins. A nonsense mutation (introducing a premature stop) can also be highly damaging, but frameshifts generally affect far more of the protein and sometimes multiple reading frames, making them especially disruptive. Details and reasoning
- Frameshift mutations: Insertion or deletion of nucleotides not in multiples of three shifts the codon reading frame. This changes almost all downstream amino acids, typically producing a truncated, nonfunctional protein or a severely altered one. They can completely destroy protein function and are often detrimental to cell viability, especially if the affected gene encodes a essential protein. This broad cascading effect makes frameshifts particularly dangerous. [general genetics knowledge]
- Nonsense mutations: A single-base change that converts a codon into a stop codon leads to early termination of translation. The resulting truncated protein is usually nonfunctional and can be deleterious, particularly for essential proteins. However, because only the length up to the premature stop is affected, some residual function or alternative splicing might mitigate impact in some contexts. [general genetics knowledge]
- Missense mutations: Replace one amino acid with another; the effect depends on the role of the substituted residue. Some missense mutations are benign or only mildly deleterious, while others severely disrupt protein structure or function. In many cases the impact is limited to one protein, not the entire proteome. [general genetics knowledge]
- Silent (synonymous) mutations: Do not change the amino acid sequence and often have little functional impact, though they can affect expression or splicing in rare cases. They are typically the least harmful among these categories. [general genetics knowledge]
- Point mutations in coding regions can be less harmful than frameshifts or nonsense mutations, but the exact outcome depends on codon position and the nature of the change. First-position changes are more likely to alter amino acids; third-position changes are more often synonymous. Yet, frameshifts/timing of stop codons generally dominate in terms of potential harm. [general genetics knowledge]
If you can share the specific mutation options you’re comparing (for example: deletion of one nucleotide, deletion of three nucleotides, substitution of one nucleotide, nonsense mutation, frameshift mutation, etc.), I can give a precise ranking for those choices in a cellular context.