What about the Ensembl Variant Effect Predictor (VEP). It allows you to input a VCF file and get a list of the genes/transcripts affected, the amino acid change (where relevant) along with SIFT and Polyphen scores and protein domains hit, tells you if the variants are already known and gives you their ID and can give you publications where the variant was seen, allows you to show or even filter by population frequency (in species where this data is available) as well as a bunch of other options. It's available as a standalone perl script which can be used offline if you set up a species cache, and as a simple web tool, although the web tool is only for ≤750 variants so wouldn't be suitable for whole genome calls.

using ANNOVAR locally you'll be able to annotate your variants using virtually any UCSC's track, plus some other useful resources as described on the web. for instance, mining for allele frequencies on 1000genomes, ESP or COSMIC has always helped us in our experiments.

Use GeneTalk to analyze human variants and talk about it.

• register at www.gene-talk.de for free
• upload VCF files onto your account
• your VCF files will be annotated and during the preprocessing step a quality assesment will be performed (if file contains more than 10.000 lines)
• filter your file with the filter tools
• take a look at annotations, comment or rate them according to medical relevance and scientific eveidence, create annotations on questionable variants
• take a look at the gene where that has a questinable variant, see if experts are available that might help you in interpreting the variant.
• share your expertise with the community or ask experts

in the following white paper you will find more information about the platform and some of its tools and features: Documentation Area at GeneTalk

• First Steps with GeneTalk
• Working with Annotations
• Compound heterozygous filtering