ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.454C>T (p.Arg152Cys)

gnomAD frequency: 0.00001  dbSNP: rs200621180
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001973364 SCV002256239 likely pathogenic not provided 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 152 of the ALPL protein (p.Arg152Cys). This variant is present in population databases (rs200621180, gnomAD 0.002%). This missense change has been observed in individual(s) with hypophosphatasia (PMID: 22014174, 23791648, 32066479, 32160374). ClinVar contains an entry for this variant (Variation ID: 1470828). 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ALPL protein function. Experimental studies have shown that this missense change affects ALPL function (PMID: 32160374). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002276963 SCV002564761 uncertain significance Osteogenesis imperfecta 2018-09-01 criteria provided, single submitter clinical testing
GeneDx RCV001973364 SCV002588071 uncertain significance not provided 2022-10-26 criteria provided, single submitter clinical testing Published functional studies suggest a damaging effect (mild reduction of activity, no additional functional studies (Del Angel et al., 2020); This variant is associated with the following publications: (PMID: 22014174, 32160374, 28127875, 35320273, 32066479, 31793067, 23791648)
Fulgent Genetics, Fulgent Genetics RCV002479619 SCV002790847 likely pathogenic Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2022-03-29 criteria provided, single submitter clinical testing
Baylor Genetics RCV003464338 SCV004194374 likely pathogenic Adult hypophosphatasia 2024-03-27 criteria provided, single submitter clinical testing

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