Thanks, Lori - that did let me troubleshoot successfully. I did just put in a github issue with a request to see the system call - that was really useful once you showed me how to do it using debugonce.

I should probably update to VEP v90 soon, but perhaps it's also useful to let you know where I stumbled: it seems simple to build in a test within VEPParam that would prevent this mysterious error.

It turns out that the default host used by the bioc module useastdb.ensembl.org) does not support anything other than the current or current minus 1 versions (according to https://www.ensembl.org/info/data/mysql.html), and gives a very uninformative error when you try to use an older version of the vep script, whether on command line or through R/Bioc.  The default host for the command-line vep script is different ensembldb.ensembl.org) - that's why I didn't replicate the error on the command line. Using ensembldb.ensembl.org as host instead fixes the issue.

I've given details below - does that work for you, or should I put this into a github issue?

So, while this fails with a mysterious error (that was what made me suspect my vep/perl installation):

library(ensemblVEP)
file <- system.file("extdata", "ex2.vcf", package="VariantAnnotation")
myparam88a <- VEPParam( version=88, dataformat=c(vcf=TRUE)) 
vcf88a <- ensemblVEP(file, param=myparam88a)

#Can't use an undefined value as an ARRAY reference at #/home/jayoung/malik_lab_shared/perl/ensembl/modules/Bio/EnsEMBL/Registry.pm line 2546.
#Error in .io_check_exists(path(con)) : file(s) do not exist:
#  '/tmp/Rtmpi8eJw2/file52c81bd6649'

when I specify a different host it works fine:

myparam88b <- VEPParam( version=88, dataformat=c(vcf=TRUE), database=c(host="ensembldb.ensembl.org")) 
vcf88b <- ensemblVEP(file, param=myparam88b)

Would it be possible to change the default host when older versions of VEP are specified?  I didn't expect that to be an issue, because on my real data I was using a local cached database and didn't think I was contacting any host at all.  The same fix works on my data, though, so I'm happy:

tempVEPcacheDir <- "/fh/fast/malik_h/grp/public_databases/Ensembl/VariantEffectPredictorCache"
tempVEPpluginsDir <- "/fh/fast/malik_h/grp/public_databases/Ensembl/VariantEffectPredictorCache/plugins"

## this fails: 
myparamsYeast88a <- VEPParam( version=88,
                            input=c(species="saccharomyces_cerevisiae"), 
                            cache=c(cache=TRUE, dir=tempVEPcacheDir,
                                dir_cache=tempVEPcacheDir, dir_plugins=tempVEPpluginsDir),
                            database=c(database=FALSE),
                            dataformat=c(vcf=TRUE) ) 
tempTest88a <- ensemblVEP(testFile, myparamsYeast88a) 
#Can't use an undefined value as an ARRAY reference at #/home/jayoung/malik_lab_shared/perl/ensembl/modules/Bio/EnsEMBL/Registry.pm line 2546.
#Error in .io_check_exists(path(con)) : file(s) do not exist:
#  '/tmp/RtmpxuFFsr/file560c5748392c'

## this works:
myparamsYeast88b <- VEPParam( version=88,
                            input=c(species="saccharomyces_cerevisiae"), 
                            cache=c(cache=TRUE, dir=tempVEPcacheDir,
                                dir_cache=tempVEPcacheDir, dir_plugins=tempVEPpluginsDir),
                            database=c(database=FALSE, host="ensembldb.ensembl.org"),
                            dataformat=c(vcf=TRUE) ) 
tempTest88b <- ensemblVEP(testFile, myparamsYeast88b) 

Session info is below (truncated - does github really only allow 5000 chars in a reply?). Thanks for the quick response - it's nice to have this figured out already.

Janet

---------

sessionInfo()
R version 3.4.0 (2017-04-21)
Platform: x86_64-pc-linux-gnu (64-bit)
Running under: Ubuntu 14.04.2 LTS

other attached packages:
[1] ensemblVEP_1.20.1          VariantAnnotation_1.22.3
[3] Rsamtools_1.28.0           Biostrings_2.44.2         
[5] XVector_0.16.0             SummarizedExperiment_1.6.0
[7] DelayedArray_0.2.0         matrixStats_0.52.2        
[9] Biobase_2.36.0             GenomicRanges_1.28.4      
[11] GenomeInfoDb_1.12.0        IRanges_2.10.3            
[13] S4Vectors_0.14.0           BiocGenerics_0.22.0