RPGRIP1 A547S - GET-Evidence



(RPGRIP1 Ala547Ser)

Short summary

Probably benign. Implicated in causing autosomal recessive cone-rod dystrophy, but a later report found the same incidence in controls and concludes it is not causal.

Variant evidence
Computational 2

Polyphen 2 predicts benign effect, amino acid change is not considered disruptive.

Functional -
Case/Control 1

Polymorphism is common in controls.

See Booij JC et al. 2005 (16272259).

Familial -1

Familial data from multiple families associated it with autosomal recessive cone-rod dystrophy.

See Hameed A et al. 2003 (12920076).

Clinical importance
Severity -
Treatability -
Penetrance -


Low clinical importance, Uncertain benign

(The "low clinical importance, uncertain" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary

This gene is associated with the disease — the families from Hameed et al. are likely to have had some other causal mutation that impacts this gene that is highly linked to this variant.

Allele frequency

  • T @ chr14:21790040: 23.2% (2257/9720) in EVS
  • T @ chr14:20859879: 21.9% (28/128) in GET-Evidence
  • Frequency shown in summary reports: 23.2% (2257/9720)


Hameed A, Abid A, Aziz A, Ismail M, Mehdi SQ, Khaliq S. Evidence of RPGRIP1 gene mutations associated with recessive cone-rod dystrophy. J Med Genet. 2003 Aug;40(8):616-9. PubMed PMID: 12920076; PubMed Central PMCID: PMC1735563.

In a study of ten families, one large consanguineous and two small Pakistani families are reported to have this variant homozygously associated with autosomal recessive cone-rod dystrophy. The authors mention 100 ethnically matched controls but it unclear if they tested this variant. The combined LOD for these is 6.2 (4.96 + 0.6 + 0.6).

Booij JC, Florijn RJ, ten Brink JB, Loves W, Meire F, van Schooneveld MJ, de Jong PT, Bergen AA. Identification of mutations in the AIPL1, CRB1, GUCY2D, RPE65, and RPGRIP1 genes in patients with juvenile retinitis pigmentosa. J Med Genet. 2005 Nov;42(11):e67. PubMed PMID: 16272259; PubMed Central PMCID: PMC1735944.

A screen of 17 ARRP, nine LCA, and nine IRP patients and 60 controls this variant had similar allele frequencies of 14% in patients and 13% in controls. This indicates the variant is not causal.


hu025CEA - CGI sample GS01669-DNA_D02 from PGP sample 27316983
het T @ chr14:21790040


hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr14:21790040


hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het T @ chr14:21790040


hu0D879F - CGI sample GS00253-DNA_G01_200_37
het T @ chr14:21790040


hu241DEA - CGI sample GS01175-DNA_D05 from PGP sample 1205491
het T @ chr14:21790040





hu4339C0 - CGI sample GS01175-DNA_H01 from PGP sample 94797469
het T @ chr14:21790040


hu8229AE - CGI sample GS01173-DNA_A07 from PGP sample 96240009
het T @ chr14:21790040


hu9385BA - CGI sample GS00253-DNA_E01_200_37
het T @ chr14:21790040



huAE6220 - CGI sample GS00253-DNA_H01_200_37
het T @ chr14:21790040


huBEDA0B - CGI sample GS00253-DNA_C01_200_37
het T @ chr14:21790040


huC30901 - CGI sample GS00253-DNA_B01_200_37
het T @ chr14:21790040


huD37D14 - CGI sample GS01175-DNA_A04 from PGP sample 13272228
het T @ chr14:21790040


huD81F3D - CGI sample GS01173-DNA_D06 from PGP sample 69488604
het T @ chr14:21790040


huE80E3D - CGI sample GS00253-DNA_D01_200_37
het T @ chr14:21790040


huFAF983 - CGI sample GS01175-DNA_F02 from PGP sample 95788191
hom T @ chr14:21790040


huFFAD87 - CGI sample GS01669-DNA_H05 from PGP sample 10971581
het T @ chr14:21790040


GS06994 - var-GS06994-1100-36-ASM
het T @ chr14:20859880


GS07357 - var-GS07357-1100-36-ASM
het T @ chr14:20859880


GS10851 - var-GS10851-1100-36-ASM
het T @ chr14:20859880


GS18504 - var-GS18504-1100-36-ASM
hom T @ chr14:20859880


GS19017 - var-GS19017-1100-36-ASM
het T @ chr14:20859880


GS19238 - var-GS19238-1100-36-ASM
hom T @ chr14:20859880


GS19239 - var-GS19239-1100-36-ASM
het T @ chr14:20859880


GS19240 - var-GS19240-1100-36-ASM
hom T @ chr14:20859880


GS19701 - var-GS19701-1100-36-ASM
het T @ chr14:20859880


GS19704 - var-GS19704-1100-36-ASM
het T @ chr14:20859880


GS20509 - var-GS20509-1100-36-ASM
het T @ chr14:20859880


Other external references

  • rs10151259
  • GeneTests records for the RPGRIP1 gene
    Leber Congenital Amaurosis
    Cone-Rod Dystrophy, Type 13
    RPGRIP1-Related Leber Congenital Amaurosis
  • Score: 0.03 (benign)
    Web search results (5 hits -- see all)
  • GeneTests: Reviews
    Homozygous mutations (R827L, A547S) of RPGRIP1 are associated with autosomal recessive ... RPGRIP1 mutations: early photophobia, hypermetropia less than ...
  • Leber Congenital Amaurosis -- GeneReviews -- NCBI Bookshelf
    Homozygous mutations (R827L, A547S) of RPGRIP1 are associated with autosomal recessive ... RPGRIP1 mutations: early photophobia, hypermetropia less than ...
  • Leber Congenital Amaurosis
    Homozygous mutations (R827L, A547S) of RPGRIP1 are associated ... RPGRIP1 mutations: early photophobia, hypermetropia less than +7 diopters, and visual ...
  • Supplementary Table xls.1
    ... kÇkükékâkäkàkåkçkêkëkèkïkîkìkÄkÅkÉkækÆkôkökòkûkùkÿkÖkÜk¢k£k¥k₧kƒkákíkókúkñkÑkªkºk¿kk¬k½k ... 0_-;_-"ú"* "-"_-;_-@0_-;\-* #,##0_-;_-* "-"_-;8_-"ú"* #,##0.00_-;\-"ú" ...

Other in silico analyses

  • NBLOSUM100 score = –1
  • GET-Evidence autoscore = 4

Edit history

Gene search

"GENE" or "GENE A123C":

Log in