ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.782C>T (p.Pro261Leu)

gnomAD frequency: 0.00002  dbSNP: rs765149569
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000418497 SCV000530409 uncertain significance not provided 2023-03-21 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 34662886)
Fulgent Genetics, Fulgent Genetics RCV002480316 SCV002783192 uncertain significance Adult hypophosphatasia; Childhood hypophosphatasia; Infantile hypophosphatasia 2021-12-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000418497 SCV003515431 uncertain significance not provided 2022-10-09 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 261 of the ALPL protein (p.Pro261Leu). This variant is present in population databases (rs765149569, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ALPL-related conditions. ClinVar contains an entry for this variant (Variation ID: 388169). 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. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Natera, Inc. RCV001828429 SCV002094073 uncertain significance Hypophosphatasia 2019-10-28 no assertion criteria provided clinical testing

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