GUCY2D P701S - GET-Evidence

Note: This variant has not been sufficiently evaluated by a GET-Evidence editor.

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(GUCY2D Pro701Ser)

Short summary

Although other variants in this gene have been implicated in causing Leber Congenital Amaurosis, Vallespin et al. observe that this variant has a frequency in control population is not significantly different from that in patients. They conclude that this is likely a benign polymorphism and not disease-causing, but it’s possible it has a modifier effect that increases susceptibility to the disease.

Variant evidence
Computational 1

Variants in this gene cause this disease.

See unpublished research (below).

Functional -
Case/Control 1

Case-control data shows lack of significance.

See Booij JC et al. 2005 (16272259), Vallespin E et al. 2007 (18055816), unpublished research (below).


No familial evidence.

See unpublished research (below).

Clinical importance
Severity 1

May increase susceptibility

See unpublished research (below).

Treatability 2

Gene thereapy is being investigated (see GeneTests review)

See unpublished research (below).

Penetrance -


Insufficiently evaluated pathogenic

(The "insufficiently evaluated" qualifier is assigned automatically based on the above evidence and importance scores.)

Inheritance pattern


Summary of published research, and additional commentary


Total cases/controls case+ case– control+ control– p-value odds ratio
Leber Congenital Amaurosis
13 610 1 199 0.2073 4.241


Allele frequency

  • T @ chr17:7915912: 2.5% (268/10758) in EVS
  • T @ chr17:7856636: 7.0% (9/128) in GET-Evidence
  • Frequency shown in summary reports: 2.5% (268/10758)


Dharmaraj SR, Silva ER, Pina AL, Li YY, Yang JM, Carter CR, Loyer MK, El-Hilali HK, Traboulsi EK, Sundin OK, Zhu DK, Koenekoop RK, Maumenee IH. Mutational analysis and clinical correlation in Leber congenital amaurosis. Ophthalmic Genet. 2000 Sep;21(3):135-50. PubMed PMID: 11035546.

This variant is implicated in autosomal recessive Leber congenital amaurosis in several patients from diverse ethnicities.

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.

In this study a screen of 35 unrelated patients with juvenile autosomal recessive retinitis pigmentosa (ARRP), Leber’s congenital amaurosis (LCA), or juvenile isolated retinitis pigmentosa (IRP) found two ARRP patients heterozygous for this variant (it looks like they believe these patients to be compound heterozygous with an unknown variant). As this seems to related to LCA, these numbers are included into LCA numbers for case/control calculation.

Cases/controls case+ case– control+ control– p-value odds ratio
Leber Congenital Amaurosis
2 32 - - - -


Vallespin E, Cantalapiedra D, Riveiro-Alvarez R, Wilke R, Aguirre-Lamban J, Avila-Fernandez A, Lopez-Martinez MA, Gimenez A, Trujillo-Tiebas MJ, Ramos C, Ayuso C. Mutation screening of 299 Spanish families with retinal dystrophies by Leber congenital amaurosis genotyping microarray. Invest Ophthalmol Vis Sci. 2007 Dec;48(12):5653-61. PubMed PMID: 18055816.

Screening for mutations in families with this disease found that 11 / 589 patients had this variant vs. 1 / 200 controls. The authors suggest that this is a polymorphism or modifier allele rather than a disease-causing mutation.

Cases/controls case+ case– control+ control– p-value odds ratio
Leber Congenital Amaurosis
11 578 1 199 0.3132 3.787







GS18517 - var-GS18517-1100-36-ASM
het T @ chr17:7856637


GS18526 - var-GS18526-1100-36-ASM
het T @ chr17:7856637


GS18537 - var-GS18537-1100-36-ASM
het T @ chr17:7856637


GS18555 - var-GS18555-1100-36-ASM
het T @ chr17:7856637


GS18558 - var-GS18558-1100-36-ASM
het T @ chr17:7856637


GS18940 - var-GS18940-1100-36-ASM
het T @ chr17:7856637


GS19648 - var-GS19648-1100-36-ASM
het T @ chr17:7856637


GS19704 - var-GS19704-1100-36-ASM
het T @ chr17:7856637


Other external references

  • rs34598902
  • GeneTests records for the GUCY2D gene
    Leber Congenital Amaurosis
    Cone-Rod Dystrophy, Type 6
    GUCY2D-Related Leber Congenital Amaurosis
  • Score: 0.183 (benign)

Other in silico analyses

  • NBLOSUM100 score = 3
  • GET-Evidence autoscore = 3

Edit history

Gene search

"GENE" or "GENE A123C":

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