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NM_000035.4(ALDOB):c.448G>C (p.Ala150Pro) AND Inborn genetic diseases

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 24, 2021
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV004018526.1

Allele description [Variation Report for NM_000035.4(ALDOB):c.448G>C (p.Ala150Pro)]

NM_000035.4(ALDOB):c.448G>C (p.Ala150Pro)

Gene:
ALDOB:aldolase, fructose-bisphosphate B [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
9q31.1
Genomic location:
Preferred name:
NM_000035.4(ALDOB):c.448G>C (p.Ala150Pro)
Other names:
NM_000035.3(ALDOB):c.448G>C(p.Ala150Pro)
HGVS:
  • NC_000009.12:g.101427574C>G
  • NG_012387.1:g.13207G>C
  • NM_000035.4:c.448G>CMANE SELECT
  • NP_000026.2:p.Ala150Pro
  • LRG_1244t1:c.448G>C
  • LRG_1244:g.13207G>C
  • LRG_1244p1:p.Ala150Pro
  • NC_000009.11:g.104189856C>G
  • NM_000035.3:c.448G>C
  • NP_000026.2:p.A150P
  • P05062:p.Ala150Pro
Protein change:
A150P; ALA149PRO
Links:
UniProtKB: P05062#VAR_000553; OMIM: 612724.0001; dbSNP: rs1800546
NCBI 1000 Genomes Browser:
rs1800546
Molecular consequence:
  • NM_000035.4:c.448G>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Inborn genetic diseases
Identifiers:
MeSH: D030342; MedGen: C0950123

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004885753Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Pathogenic
(Nov 24, 2021) 		germlineclinical testing

PubMed (6)
[See all records that cite these PMIDs]

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Catalytic deficiency of human aldolase B in hereditary fructose intolerance caused by a common missense mutation.

Cross NC, Tolan DR, Cox TM.

Cell. 1988 Jun 17;53(6):881-5.

PubMed [citation]
PMID:
3383242

Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance.

Esposito G, Vitagliano L, Santamaria R, Viola A, Zagari A, Salvatore F.

FEBS Lett. 2002 Nov 6;531(2):152-6.

PubMed [citation]
PMID:
12417303
See all PubMed Citations (6)

Details of each submission

From Ambry Genetics, SCV004885753.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (6)

Description

The c.448G>C (p.A150P) alteration is located in exon 5 (coding exon 4) of the ALDOB gene. This alteration results from a G to C substitution at nucleotide position 448, causing the alanine (A) at amino acid position 150 to be replaced by a proline (P). Based on data from gnomAD, the C allele has an overall frequency of 0.31% (874/282528) total alleles studied. The highest observed frequency was 0.49% (627/128866) of European (non-Finnish) alleles. This mutation (also referred to as A149P) has been reported in the homozygous and compound heterozygous states in many affected patients, and is the most frequent ALDOB mutation with a frequency of up to 64% in various cohorts of patients with hereditary fructose intolerance (Cross, 1988; Santer, 2005; Davit-Spraul, 2008; Coffee, 2010). This amino acid position is not well conserved in available vertebrate species. In vitro functional studies show that protein with the p.A150P mutation demonstrates temperature-dependent structural changes and decreased enzyme activity compared to wild type protein (Esposito, 2002; Malay, 2002). This alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, this alteration is classified as pathogenic.

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

Last Updated: May 12, 2024