Today I set out to compile an exhaustive list of rare variants in PRNP which have been reported to be pathogenic. I am posting this list here as a reference. Here are some disclaimers:

  • This does not constitute an endorsement that each of these variants is indeed associated with prion disease risk - some may actually be benign. This is just a review of what has been reported in the literature.
  • The “see also” column is far from exhaustive. Many of these variants have been discussed in tens of publications.
  • I compiled this list by reading two reviews [Kong 2004, Beck 2010] and OMIM #176640 and by searching PubMed for new reports since 2010. After initial publication of this post, Simon Mead pointed out a few variants I had missed. Co-authors of [Minikel 2016] later pointed out further edits. As of the last updated date below, I think this is complete but if you know of something I missed, please leave a comment below.
  • I excluded any variants known to have an allele frequency >0.5% in at least one continental population, including 1-OPRD [Palmer 1993], and G54S, M129V, G142S, N171S, and E219K.

Last updated 2016-01-24, now contains 65 variants.

variant first report see also
P39L Bernardi 2014  
2-OPRD Beck 2001 Capellari 2002
1-OPRI Laplanche 1995 Pietrini 2003
2-OPRI Hill 2006  
3-OPRI Nishida 2004  
4-OPRI Laplanche 1995 Campbell 1996, Kaski 2011
5-OPRI Goldfarb 1991  
6-OPRI Owen 1990 Mead 2006
7-OPRI Goldfarb 1991 Lewis 2003
8-OPRI Goldfarb 1991 Laplanche 1999
9-OPRI Krasemann 1995  
12-OPRI Kumar 2011  
P84S Jones 2014  
S97N Zheng 2008  
P102L Goldgaber 1989 Hsiao 1992
P105L Yamada 1993 Yamada 1999
P105S Tunnell 2008  
P105T Rogaeva 2006 Polymenidou 2011
G114V Rodriguez 2005 Liu 2010
A117V Tateishi 1990 Hsiao 1991
129insLGGLGGYV Hinnell 2011  
G131V Panegyres 2001 Jansen 2012
S132I Hilton 2009  
A133V Rowe 2007  
Y145X Kitamoto 1993  
R148H Krebs 2005 Pastore 2005
Q160X Finckh 2000 Jayadev 2011
Y163X Revesz 2009 Mead 2013
D167G Bishop 2009  
D167N Beck 2010  
V176G Simpson 2013  
D178Efs25X Mastuzono 2013  
D178N Goldfarb 1991 Medori 1992, Goldfarb 1992
V180I Hitoshi 1993 Chasseigneaux 2006
T183A Nitrini 1997 Grasbon-Frodl 2004
H187R Butefisch 2000  
T188A Collins 2000  
T188K Finckh 2000 Roeber 2008
T188R Windl 1999 Roeber 2008, Tartaglia 2010
T193I Kotta 2006  
E196A Zhang 2014  
E196K Peoc’h 2000  
F198S Farlow 1989 Hsiao 1992
F198V Zheng 2008  
E200G Kim 2013  
E200K Goldgaber 1989 Hsiao 1991
T201S Parvez 2010  
D202G Heinemann 2008  
D202N Piccardo 1998  
V203I Peoc’h 2000  
R208C Zheng 2008  
R208H Mastrianni 1996 Capellari 2005, Roeber 2005
V210I Ripoll 1993 Pocchiari 1993, Mouillet-Richard 1999
E211D Peoc’h 2012  
E211Q Peoc’h 2000  
Q212P Piccardo 1998  
I215V Munoz-Nieto 2013  
Q217R Hsiao 1992  
Y218N Alzualde 2010  
A224V Watts 2015*  
Y226X Jansen 2010  
Q227X Jansen 2010  
M232R Hitoshi 1993 Hoque 1996
M232T Bratosiewicz 2000  
P238S Windl 1999  

* Variant is suggested to be a risk factor.