How does one predict how large of an effect on antigenic drift a substitution in the amino acid sequence of a surface protein of influenza has?
Your understanding of influenza antigenic drift is, unfortunately, hypersimplified and mostly wrong. In particular, your notion that some mutations are more important for antigenic drift because of their effects on structure is at best oversimplified.

Rather than spend many paragraphs reviewing the complex patterns involved, I'd suggest you start by carefully reading papers from people who have correlated antigenic drift with sequence change, such as 


Sequence-Based Antigenic Change Prediction by a Sparse Learning Method Incorporating Co-Evolutionary Information
Using Sequence Data To Infer the Antigenicity of Influenza Virus
Mapping the Antigenic and Genetic Evolution of Influenza Virus
The genomic and epidemiological dynamics of human influenza A virus
Selection of antigenically advanced variants of seasonal influenza viruses
Antibody landscapes after influenza virus infection or vaccination
Substitutions Near the Receptor Binding Site Determine Major Antigenic Change During Influenza Virus Evolution


This is a field that a lot of extremely smart people have been looking at extremely closely for many years; all the simple approaches have been tried already.