Deleterious or Protective? --> CADD score >20 but Odds ratio <1

Question

[Shab86]

So, I have a variant that has a CADD PHRED score of >20 but the OR is < 1. So, I am not sure whether this is a deleterious or protective variant? Any ideas on how to interpret this?

Thanks, Sabeer

Answer 1

[Kevin Blighe]

Hi, its OR is < 1 from which study design? It may be better to think of CADD scores as measures of 'functionality', and not necessarily pathogenicity. So, a variant that introduces a functional change can be either advantageous or not. Even a deleterious variant can be advantageous.

[Shab86]

Thanks Kevin for your reply! Its from a case-control design study (200k+ individuals), and that missense variant is genome-wide significant.

[Kevin Blighe]

Cool, it would be interesting if you could share the exact variant in question (?). Either way, I think that it is valid for a CADD score to be high for a protective variant.