Summary
The experimental effect of missense mutations was reasonably predictive of the effect of deletion mutations, and slightly less predictive of insertion mutations on either side that residue, though this depends on the protein (1).
Details
Similar conclusions were reached by (2):
Across 175 protein domains with in vitro fold stability measurements of indels and substitutions, substitution tolerance predicts Ala insertion tolerance similarly well after (mode r=0.281) and before a residue (r=0.240) and better predicts 1 aa deletion tolerance (mode r=0.459).
Combining with secondary structure information, this was more effective than solvent accessibility in predicting mutation effect.
1.
Topolska M, Beltran A, Lehner B. Deep indel mutagenesis reveals the impact of amino acid insertions and deletions on protein stability and function. Nature Communications. 2025;16(1). Available from: https://doi.org/10.1038/s41467-025-57510-5
2.
Tsuboyama K, Dauparas J, Chen J, Laine E, Mohseni Behbahani Y, Weinstein JJ, et al. Mega-scale experimental analysis of protein folding stability in biology and design. Nature. 2023;620(7973):434–44. Available from: https://doi.org/10.1038/s41586-023-06328-6