ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.283G>A (p.Val95Met)

gnomAD frequency: 0.00001  dbSNP: rs139811782
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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001067182 SCV001232228 pathogenic not provided 2024-10-23 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 95 of the ALPL protein (p.Val95Met). This variant is present in population databases (rs139811782, gnomAD 0.01%). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 30719581, 31641588). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 427763). 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: 32160374). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV001535923 SCV001752575 likely pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2021-06-30 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001580504 SCV001810260 likely pathogenic Childhood hypophosphatasia 2021-07-22 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002279265 SCV002564739 uncertain significance Osteogenesis imperfecta 2022-02-28 criteria provided, single submitter clinical testing
Baylor Genetics RCV003470594 SCV004194474 likely pathogenic Adult hypophosphatasia 2024-03-20 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV004568606 SCV005051899 pathogenic Infantile hypophosphatasia 2024-02-01 criteria provided, single submitter curation
Juno Genomics, Hangzhou Juno Genomics, Inc RCV001535923 SCV005871492 likely pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia criteria provided, single submitter clinical testing PM2_Supporting+PP3+PS4_Supporting+PM3+PP4
Institute of Human Genetics, University of Wuerzburg RCV000490714 SCV000579348 likely pathogenic Decreased circulating alkaline phosphatase activity no assertion criteria provided clinical testing
Natera, Inc. RCV001273158 SCV001455763 uncertain significance Hypophosphatasia 2020-09-16 no assertion criteria provided clinical testing

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