ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.395C>T (p.Ala132Val)

dbSNP: rs1558548925
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000730364 SCV000858094 likely pathogenic not provided 2017-11-27 criteria provided, single submitter clinical testing
GeneDx RCV000730364 SCV001764817 likely pathogenic not provided 2020-12-01 criteria provided, single submitter clinical testing Reported in the heterozygous state in an individual with adult onset hypophosphatasia (Watanabe et al., 2001); Published functional studies demonstrate a damaging effect on ALPL protein function (Orimo et al., 2008); Not observed in large population cohorts (Lek et al., 2016); Missense variants at the same residue and in nearby residues reported in the Human Gene Mutation Database (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 18455459, 30655187, 19500388, 11834095)
Labcorp Genetics (formerly Invitae), Labcorp RCV000730364 SCV002292989 pathogenic not provided 2024-12-03 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 132 of the ALPL protein (p.Ala132Val). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 11834095, 32160374). This variant is also known as C571T (Ala115Val). ClinVar contains an entry for this variant (Variation ID: 594951). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt ALPL protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects ALPL function (PMID: 18455459, 19500388). This variant disrupts the p.Ala132 amino acid residue in ALPL. Other variant(s) that disrupt this residue have been observed in individuals with ALPL-related conditions (PMID: 32160374; internal data), which suggests that this may be a clinically significant amino acid residue. For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV002493325 SCV002803912 likely pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2022-05-09 criteria provided, single submitter clinical testing
Baylor Genetics RCV003465663 SCV004193730 likely pathogenic Adult hypophosphatasia 2023-01-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV001825460 SCV002094053 likely pathogenic Hypophosphatasia 2021-10-08 no assertion criteria provided clinical testing

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