I hope you have a lot of good positive control variants / samples for troubleshooting.
For example, I would have the following concerns:
1) If you are doing targeted sequencing, you may have more of a need to have specialized variant calling. For example, GATK can do some weird things in high coverage regions (like >1000x), and I think Figure in the Warden et al. 2014 paper kind of illustrates my point (although perhaps more so for samtools than GATK):
Not sure how much a difference looking for unique sequences in reads would make, but I'm assuming that requires no nearby SNPs.
Also, in the figure above, please notice the scale of the y-axis is different (particularly for the left plot with the most focused sequencing).
2) I am a cystic fibrosis carrier, and I had reports from some companies that falsely identified me as not being a carrier (even though you could verify the variant in the raw data):
https://github.com/cwarden45/DTC_Scripts/tree/master/Genos_Exome (please scroll to the bottom for alignment screenshot: also true for GET-Evidence report for Veritas WGS data)
So, carefully considering all steps in the analysis is important. I like the idea of specializing in assessment for a particular disease / gene (for clinical reporting / interpretation), but I don't there is way to quickly be confident your strategy will be without problems (you need to spend a substantial amount of time critically assessing your ideas, and still expect a need for troubleshooting / support after providing something in the clinic).
I realize this is probably for research purposes, and I think you have a good point about needing some way to assess each sample (preferably in a way that can be done without coding). In the research setting, I think you should definitely expect some need to modify strategies. In the clinical (or DTC) setting, you need to be required to have access to your raw data, but I can see how this could cause issues with physicians (at least in settings where they have to be able to make decisions with a limited amount of available time).