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NM_001378373.1(MBL2):c.154C>T (p.Arg52Cys) AND Mannose-binding lectin deficiency

Clinical significance:Pathogenic (Last evaluated: Dec 11, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_001378373.1(MBL2):c.154C>T (p.Arg52Cys)]

NM_001378373.1(MBL2):c.154C>T (p.Arg52Cys)

MBL2:mannose binding lectin 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_001378373.1(MBL2):c.154C>T (p.Arg52Cys)
Other names:
  • NC_000010.11:g.52771482G>A
  • NG_008196.1:g.5219C>T
  • NM_000242.3:c.154C>T
  • NM_001378373.1:c.154C>TMANE SELECT
  • NM_001378374.1:c.154C>T
  • NP_000233.1:p.Arg52Cys
  • NP_001365302.1:p.Arg52Cys
  • NP_001365303.1:p.Arg52Cys
  • LRG_154t1:c.154C>T
  • LRG_154:g.5219C>T
  • NC_000010.10:g.54531242G>A
  • NG_008196.1:p.Arg52Cys
  • NM_000242.2:c.154C>T
  • P11226:p.Arg52Cys
Protein change:
Genetic Testing Registry (GTR): GTR000509360; UniProtKB: P11226#VAR_008543; OMIM: 154545.0003; dbSNP: rs5030737
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000242.3:c.154C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378373.1:c.154C>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001378374.1:c.154C>T - missense variant - [Sequence Ontology: SO:0001583]


Mannose-binding lectin deficiency
Mannose-binding protein deficiency; MBP DEFICIENCY; MBL DEFICIENCY; See all synonyms [MedGen]
MONDO: MONDO:0013714; MedGen: C3280586; OMIM: 614372

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000035690OMIMno assertion criteria providedPathogenic
(Aug 1, 2006)
germlineliterature only

PubMed (2)
[See all records that cite these PMIDs]

SCV000914462Illumina Laboratory Services, Illuminacriteria provided, single submitter
(Dec 11, 2018)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing
not providedgermlinenot providednot providednot providednot providednot providednot providedliterature only



Evidence for an association between mannose-binding lectin 2 (MBL2) gene polymorphisms and pre-term birth.

Bodamer OA, Mitterer G, Maurer W, Pollak A, Mueller MW, Schmidt WM.

Genet Med. 2006 Aug;8(8):518-24.

PubMed [citation]

Defective activities, but not secretions, resulting from gene point mutations of human mannan-binding lectin.

Liu Y, Liu FL, Bai ZJ, Zhao N, Zhang LY, Lu X, Chen ZL.

Mol Med Rep. 2012 Apr;5(4):1121-7. doi: 10.3892/mmr.2012.782. Epub 2012 Feb 6.

PubMed [citation]
See all PubMed Citations (5)

Details of each submission

From OMIM, SCV000035690.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedliterature only PubMed (2)


Madsen et al. (1994) identified a third variant allele, the 'D' allele (rs5030737), in the collagen region of MBL2, and suggested that this variant could explain cases of MBL deficiency (MBLD; 614372) not determined by the other variants. The frequency of allele D was 0.05 in both African and Caucasian populations, but the allele was absent in Eskimos.

Bodamer et al. (2006) genotyped 5 common polymorphisms, including the B, C, and D variants, of the MBL2 gene in 102 infants born before 36 weeks' gestation and 102 infants born at full term and found that the frequency of the D allele was significantly higher in preterm infants compared to term infants (p = 0.04).

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenot providednot providednot providednot providednot providednot providednot providednot provided

From Illumina Laboratory Services, Illumina, SCV000914462.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)


The MLB2 c.154C>T (p.Arg52Cys) missense variant, commonly referred to as the "D" allele, has been described in at least one study in individuals with recurrent infections and low serum MBP levels in which it was found in a compound heterozygous state with another missense variant in one individual with a very low serum MBP level and in a homozygous state in another individual with no detectable serum MBP level (Summerfield et al. 1995). The p.Arg52Cys variant has also been investigated in healthy unrelated individuals with low or undetectable MBP levels (Madsen et al. 1994; Babovic-Vuksanovic et al. 1999) and found at a frequency of 0.05 in both the African and Caucasian populations in both a compound heterozygous state and a heterozygous state. Functional studies by Liu et al. (2012) showed that the p.Arg52Cys variant did not affect gene transcription or protein secretion, but did result in a lower level of oligomerization, a loss of ability to bind mannan, a reduced ability to bind to MASP1 and MASP2 and failed to activate the complement system. However, it should be noted that MBL deficiency is very common. The p.Arg52Cys variant is reported at a frequency of is 0.11111 in the Finnish population of the 1000 Genomes Project. While the allele frequency for this variant appears to be high, multiple studies referenced in this paragraph have shown a significant over-representation of this variant in individuals with low levels of mannose-binding lectin as compared to controls. Many individuals who carry MBL2 variants classified as pathogenic do not develop clinical complications. Based on the evidence, the p.Arg52Cys variant is classified as pathogenic for mannose-binding lectin deficiency. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.

OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Mar 4, 2023