ABCA4 R943Q - GET-Evidence



(ABCA4 Arg943Gln)

Short summary

This is a polymorphism in a gene associated with Stargardt disease. Although it has a slight detectable effect in functional study, it is common in control groups and is not believed to have any significant pathogenic effect.

Variant evidence
Computational -1

Polyphen 2 predicts damaging effect

Functional -1

Slight functional effect

See Suárez T et al. 2002 (11919200).

Case/Control 1

High incidence in control group

See Allikmets R et al. 1997 (9295268).

Familial -
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


Allele frequency

  • T @ chr1:94512565: 3.2% (340/10758) in EVS
  • T @ chr1:94285152: 3.9% (5/128) in GET-Evidence
  • Frequency shown in summary reports: 3.2% (340/10758)


Allikmets R, Shroyer NF, Singh N, Seddon JM, Lewis RA, Bernstein PS, Peiffer A, Zabriskie NA, Li Y, Hutchinson A, Dean M, Lupski JR, Leppert M. Mutation of the Stargardt disease gene (ABCR) in age-related macular degeneration. Science. 1997 Sep 19;277(5333):1805-7. PubMed PMID: 9295268.

These authors investigated whether variants in this gene (associated with Stargardt disease (SD)) contribute to age-related macular degeneration (AMD). The authors found no increased incidence in AMD patients (6/127, 4.7%) or SD patients (4/47, 9.5%) compared to controls (13/80, 16.25%), supporting a nonpathogenic effect.

In fact, this is a significant difference in the other direction — a p=0.0067 for the AMD vs. control set, p = 0.0096 for the combined AMD + SD set. This may mean the control population was not ethnically matched well with the disease cases. Alternatively, the variant could have some protective effect for AMD — the authors do not make this hypothesis, however.

Suárez T, Biswas SB, Biswas EE. Biochemical defects in retina-specific human ATP binding cassette transporter nucleotide binding domain 1 mutants associated with macular degeneration. J Biol Chem. 2002 Jun 14;277(24):21759-67. Epub 2002 Mar 27. PubMed PMID: 11919200.

This group reports that the R943Q mutation has small (but detectable) reduction in nucleotidase activity and nucleotide binding affinity.


hu04FD18 - CGI sample GS00253-DNA_F01_200_37
het T @ chr1:94512565


hu0D879F - CGI sample GS00253-DNA_G01_200_37
het T @ chr1:94512565







GS12004 - var-GS12004-1100-36-ASM
het T @ chr1:94285153


Other external references

  • rs1801581
  • GeneTests records for the ABCA4 gene
    Age-related macular degeneration
    ABCA4-Related Retinitis Pigmentosa
    ABCA4-Related Stargardt Disease 1
    Age-Related Macular Degeneration 2
    Cone-Rod Dystrophy, Type 3
    Retinitis Pigmentosa, Autosomal Recessive
    Stargardt Disease, Autosomal Recessive
  • Score: 0.922 (probably damaging)

Other in silico analyses

  • NBLOSUM100 score = 0
  • GET-Evidence autoscore = 5

Edit history

Gene search

"GENE" or "GENE A123C":

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