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

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Interpretation:
Pathogenic​

Review status:
criteria provided, multiple submitters, no conflicts
Submissions:
16 (Most recent: Mar 28, 2019)
Last evaluated:
Dec 22, 2018
Accession:
VCV000000464.3
Variation ID:
464
Description:
single nucleotide variant
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NM_000035.4(ALDOB):c.448G>C (p.Ala150Pro)

Allele ID
15503
Variant type
single nucleotide variant
Variant length
1 bp
Cytogenetic location
9q31.1
Genomic location
9: 101427574 (GRCh38) GRCh38 UCSC
9: 104189856 (GRCh37) GRCh37 UCSC
HGVS
Nucleotide Protein Molecular
consequence
NC_000009.12:g.101427574C>G
NC_000009.11:g.104189856C>G
LRG_1244t1:c.448G>C LRG_1244p1:p.Ala150Pro
... more HGVS
Protein change
A150P
Other names
NM_000035.3(ALDOB):c.448G>C(p.Ala150Pro)
Functional consequence
-
Global minor allele frequency (GMAF)
0.00180 (G)

Allele frequency
The Genome Aggregation Database (gnomAD) 0.00420
Trans-Omics for Precision Medicine (TOPMed) 0.00268
Exome Aggregation Consortium (ExAC) 0.00270
1000 Genomes Project 0.00180
The Genome Aggregation Database (gnomAD), exomes 0.00295
Links
ClinGen: CA339810
UniProtKB: P05062#VAR_000553
OMIM: 612724.0001
dbSNP: rs1800546
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Aggregate interpretations per condition

Interpreted condition Interpretation Number of submissions Review status Last evaluated Variation/condition record
Pathogenic 13 criteria provided, multiple submitters, no conflicts Dec 22, 2018 RCV000000493.13
Pathogenic 3 criteria provided, multiple submitters, no conflicts Jul 17, 2018 RCV000224056.5

Clinical features observed in individuals with this variant

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Gene OMIM ClinGen Gene Dosage Sensitivity Curation Variation viewer Related variants
HI score Help TS score Help Within gene All
ALDOB - - GRCh38
GRCh37
127 159

Submitted interpretations and evidence

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Interpretation
(Last evaluated)
Review status
(Assertion criteria)
Condition
(Inheritance)
Submitter Supporting information
Pathogenic
(Dec 29, 2015)
criteria provided, single submitter
Method: clinical testing
Hereditary fructosuria
Allele origin: unknown
Counsyl
Accession: SCV000485176.1
Submitted: (Nov 23, 2016)
Evidence details
Pathogenic
(Oct 02, 2014)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics
Accession: SCV000280999.2
Submitted: (Oct 05, 2017)
Evidence details
Pathogenic
(Jul 10, 2017)
criteria provided, single submitter
Method: clinical testing
Not Provided
Allele origin: germline
GeneDx
Accession: SCV000322438.6
Submitted: (Nov 28, 2017)
Evidence details
Comment:
The A150P variant is the most common ALDOB pathogenic variant among individuals of European ancestry; it has been observed numerous times (also reported as A149P ... (more)
Pathogenic
(Aug 21, 2017)
criteria provided, single submitter
Method: clinical testing
Hereditary fructosuria
Allele origin: germline
Integrated Genetics/Laboratory Corporation of America
Accession: SCV000693962.1
Submitted: (Jan 25, 2018)
Evidence details
Publications
PubMed (2)
Comment:
Variant summary: The ALDOB c.448G>C (p.Ala150Pro) variant involves the alteration of a conserved nucleotide. 5/5 in silico tools predict a damaging outcome for this variant. ... (more)
Pathogenic
(May 31, 2018)
criteria provided, single submitter
Method: curation
Hereditary fructosuria
Allele origin: unknown
SIB Swiss Institute of Bioinformatics
Accession: SCV000803454.1
Submitted: (Jun 13, 2018)
Evidence details
Publications
PubMed (6)
Comment:
This variant is interpreted as a Pathogenic, for Fructose intolerance, hereditary, in Autosomal Recessive manner. The following ACMG Tag(s) were applied: PM2 => Absent from ... (more)
Pathogenic
(Jul 17, 2018)
criteria provided, single submitter
Method: clinical testing
not provided
Allele origin: germline
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics
Accession: SCV000230833.5
Submitted: (Sep 19, 2018)
Evidence details
Other databases
http://www.egl-eurofins.com/em...
Pathogenic
(Oct 31, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary fructosuria
Allele origin: unknown
Fulgent Genetics,Fulgent Genetics
Accession: SCV000894461.1
Submitted: (Nov 14, 2018)
Evidence details
Publications
PubMed (1)
DOI: 10.1038/gim.2015.30
Pathogenic
(May 17, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary fructosuria
Allele origin: germline
Illumina Clinical Services Laboratory,Illumina
Accession: SCV000476066.3
Submitted: (Feb 01, 2019)
Evidence details
Publications
PubMed (5)
Comment:
The ALDOB c.448G>C (p.Ala150Pro) variant is well-documented as one of the most common variants among patients with hereditary fructose intolerance in European and North American ... (more)
Pathogenic
(Dec 22, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary fructosuria
Allele origin: germline
Invitae
Accession: SCV000752027.3
Submitted: (Mar 28, 2019)
Evidence details
Publications
PubMed (7)
Comment:
This sequence change replaces alanine with proline at codon 150 of the ALDOB protein (p.Ala150Pro). The alanine residue is moderately conserved and there is a ... (more)
Pathogenic
(Mar 21, 2018)
criteria provided, single submitter
Method: clinical testing
Hereditary fructosuria
(Autosomal recessive inheritance)
Allele origin: germline
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine
Accession: SCV000711745.1
Submitted: (Mar 21, 2019)
Evidence details
Publications
PubMed (4)
Comment:
The p.Ala150Pro variant in ALDOB (frequently referred to as p.Ala149Pro) is the most common hereditary fructose intolerance (HFI) allele, accounting for approxi mately half of ... (more)
Pathogenic
(Aug 01, 2008)
no assertion criteria provided
Method: literature only
FRUCTOSE INTOLERANCE
Allele origin: germline
OMIM
Accession: SCV000020642.2
Submitted: (Dec 30, 2010)
Evidence details
Publications
PubMed (6)
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Hereditary fructosuria
Allele origin: germline
DLE - Diagnosticos Laboratoriais Especializados
Accession: SCV000077515.1
Submitted: (Mar 16, 2017)
Evidence details
Other databases
http://www.ctgt.net/disorder/s...
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Hereditary fructosuria
Allele origin: germline
HFI Laboratory at Boston University,Boston University
Accession: SCV000067374.1
Submitted: (Mar 15, 2017)
Evidence details
Publications
PubMed (1)
Pathogenic
(Oct 07, 2015)
no assertion criteria provided
Method: literature only
Hereditary fructosuria
Allele origin: germline
GeneReviews
Accession: SCV000257571.1
Submitted: (Oct 07, 2015)
Evidence details
Publications
PubMed (7)
Other databases
http://www.ncbi.nlm.nih.gov/bo...
Pathogenic
(-)
no assertion criteria provided
Method: clinical testing
Hereditary fructosuria
Allele origin: germline
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare
Accession: SCV000323150.1
Submitted: (Oct 10, 2016)
Evidence details
not provided
(-)
no assertion provided
Method: phenotyping only
Hereditary fructosuria
Allele origin: paternal
GenomeConnect, ClinGen
Accession: SCV000840266.1
Submitted: (Mar 13, 2018)
Evidence details
Comment:
GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical ... (more)

Citations for this variant

Title Author Journal Year Link
Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria. Nykamp K Genetics in medicine : official journal of the American College of Medical Genetics 2017 PMID: 28492532
Hereditary fructose intolerance mimicking a biochemical phenotype of mucolipidosis: A review of the literature of secondary causes of lysosomal enzyme activity elevation in serum. Ferreira CR American journal of medical genetics. Part A 2017 PMID: 27797444
Hereditary fructose intolerance in Brazilian patients. Valadares ER Molecular genetics and metabolism reports 2015 PMID: 26937407
Hereditary Fructose Intolerance Baker P II - 2015 PMID: 26677512
Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Richards S Genetics in medicine : official journal of the American College of Medical Genetics 2015 PMID: 25741868
Integration of PCR-Sequencing Analysis with Multiplex Ligation-Dependent Probe Amplification for Diagnosis of Hereditary Fructose Intolerance. Ferri L JIMD reports 2012 PMID: 23430936
Increased prevalence of mutant null alleles that cause hereditary fructose intolerance in the American population. Coffee EM Journal of inherited metabolic disease 2010 PMID: 20033295
Secondary disorders of glycosylation in inborn errors of fructose metabolism. Quintana E Journal of inherited metabolic disease 2009 PMID: 19768653
Hereditary fructose intolerance: frequency and spectrum mutations of the aldolase B gene in a large patients cohort from France--identification of eight new mutations. Davit-Spraul A Molecular genetics and metabolism 2008 PMID: 18541450
Aldolase B mutations and prevalence of hereditary fructose intolerance in a Polish population. Gruchota J Molecular genetics and metabolism 2006 PMID: 16406649
The spectrum of aldolase B (ALDOB) mutations and the prevalence of hereditary fructose intolerance in Central Europe. Santer R Human mutation 2005 PMID: 15880727
Structure of the thermolabile mutant aldolase B, A149P: molecular basis of hereditary fructose intolerance. Malay AD Journal of molecular biology 2005 PMID: 15733923
The temperature dependence of activity and structure for the most prevalent mutant aldolase B associated with hereditary fructose intolerance. Malay AD Archives of biochemistry and biophysics 2002 PMID: 12464284
Structural and functional analysis of aldolase B mutants related to hereditary fructose intolerance. Esposito G FEBS letters 2002 PMID: 12417303
Molecular analysis of the aldolase B gene in patients with hereditary fructose intolerance from Spain. Sánchez-Gutiérrez JC Journal of medical genetics 2002 PMID: 12205126
Mutation analysis in Turkish patients with hereditary fructose intolerance. Dursun A Journal of inherited metabolic disease 2001 PMID: 11757579
Association of the widespread A149P hereditary fructose intolerance mutation with newly identified sequence polymorphisms in the aldolase B gene. Brooks CC American journal of human genetics 1993 PMID: 8096362
Molecular analysis of aldolase B genes in hereditary fructose intolerance. Cross NC Lancet (London, England) 1990 PMID: 1967768
Molecular analysis of aldolase B genes in the diagnosis of hereditary fructose intolerance in the United Kingdom. Cross NC The Quarterly journal of medicine 1989 PMID: 2623136
Catalytic deficiency of human aldolase B in hereditary fructose intolerance caused by a common missense mutation. Cross NC Cell 1988 PMID: 3383242
Isolation and characterization of a mutant liver aldolase in adult hereditary fructose intolerance. Identification of the enzyme variant by radioassay in tissue biopsy specimens. Cox TM The Journal of clinical investigation 1983 PMID: 6348085
http://www.ctgt.net/disorder/smith-mccort-dysplasia-smc - - - -
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ALDOB - - - -
http://www.ncbi.nlm.nih.gov/books/NBK333439/ - - - -

Record last updated Oct 27, 2019