MBL2 G54D - GET-Evidence



(MBL2 Gly54Asp)

Short summary

This variant is associated with mannose binding protein deficiency which leads to impaired complement system immune response to mannose-rich pathogens. Patients homozygous for this allele or compound heterozygous are likely to have increased susceptibility to infection, but Hellemann et al. report heterosis for intensive care outcomes in heterozygous subjects. The wild-type version of this gene is known as variant allele A, while this is called variant allele B. See R52C (variant D) and G57E (variant C).

Variant evidence
Computational 2

Other mutations in the gene are associated with disease, NBLOSUM = 3

See Garred P et al. 1995 (7564730), Hibberd ML et al. 1999 (10199352).

Functional -
Case/Control 5

Combined data has very low p-value

See Garred P et al. 1995 (7564730), Hibberd ML et al. 1999 (10199352).


No familial data.

See unpublished research (below).

Clinical importance
Severity 2

Increased susceptibility to infection.

Treatability 2

No standard treatment. Behavioral changes and increased surveillance may address increased susceptibility to disease.

Penetrance 3

Assuming the suspected immunodeficiency studied by Hibberd et al. has an incidence of around 1 in 200 to 1 in 500, their data is consistent with moderate penetrance (only one individual in 123 controls homozygous for the variant).

See Hibberd ML et al. 1999 (10199352).



Low clinical importance, Likely pathogenic

(The "low clinical importance, likely" 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
Mannose-Binding Lectin Deficiency
39 454 6 500 0.0000 7.159


Allele frequency

  • T @ chr10:54531235: 10.4% (1118/10758) in EVS
  • T @ chr10:54201240: 7.0% (9/128) in GET-Evidence
  • Frequency shown in summary reports: 10.4% (1118/10758)


Garred P, Madsen HO, Hofmann B, Svejgaard A. Increased frequency of homozygosity of abnormal mannan-binding-protein alleles in patients with suspected immunodeficiency. Lancet. 1995 Oct 7;346(8980):941-3. PubMed PMID: 7564730.

A study of patients with suspected immunodeficiency found a higher number of homozygous and compound heterozygous patients with abnormal mannan-binding protein (MBP) alleles (variants B, C, and D). In the case group of 227 patients, 12 patients were homozygous for B and 6 were compound heterozygous for B/C or B/D. One patient in the control population of 123 patients was homozygous or compound heterozygous.

Cases/controls case+ case– control+ control– p-value odds ratio
Mannose-Binding Lectin Deficiency
18 209 1 123 0.0050 10.593


Hibberd ML, Sumiya M, Summerfield JA, Booy R, Levin M. Association of variants of the gene for mannose-binding lectin with susceptibility to meningococcal disease. Meningococcal Research Group. Lancet. 1999 Mar 27;353(9158):1049-53. PubMed PMID: 10199352.

A study of the frequency of MBL2 variants was made comparing children meningococcal disease with controls. Of 266 patients, 8 were homozygous for G54D and 13 were compound heterozygous for G54D and either R52C or G57E. Of 382 controls, 1 was homozygous and 4 were compound heterozygous for G54D.

Cases/controls case+ case– control+ control– p-value odds ratio
Mannose-Binding Lectin Deficiency
21 245 5 377 0.0000 6.463


Hellemann D, Larsson A, Madsen HO, Bonde J, Jarløv JO, Wiis J, Faber T, Wetterslev J, Garred P. Heterozygosity of mannose-binding lectin (MBL2) genotypes predicts advantage (heterosis) in relation to fatal outcome in intensive care patients. Hum Mol Genet. 2007 Dec 15;16(24):3071-80. Epub 2007 Sep 14. PubMed PMID: 17872904.



hu034DB1 - CGI sample GS00253-DNA_A02_200_37
het T @ chr10:54531235


hu38168C - CGI sample GS01173-DNA_H06 from PGP sample 91708424
het T @ chr10:54531235


huA0E089 - CGI sample GS01175-DNA_B04 from PGP sample 88590671
het T @ chr10:54531235


huB1FD55 - CGI sample GS01173-DNA_B07 from PGP sample 61499538
het T @ chr10:54531235


GS19648 - var-GS19648-1100-36-ASM
het T @ chr10:54201241


GS19670 - var-GS19670-1100-36-ASM
het T @ chr10:54201241


GS19703 - var-GS19703-1100-36-ASM
het T @ chr10:54201241


Other external references

  • rs1800450
  • Score: 0.994 (probably damaging)

Other in silico analyses

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

Edit history

Gene search

"GENE" or "GENE A123C":

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