ClinVar Miner

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

gnomAD frequency: 0.00001  dbSNP: rs139811782
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001067182 SCV001232228 pathogenic not provided 2023-09-22 criteria provided, single submitter clinical testing Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ALPL protein function. 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). 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 2023-09-11 criteria provided, single submitter clinical testing
Institute of Human Genetics, University of Wuerzburg RCV000490714 SCV000579348 likely pathogenic Low alkaline phosphatase no assertion criteria provided clinical testing
Natera, Inc. RCV001273158 SCV001455763 uncertain significance Hypophosphatasia 2020-09-16 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.