ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.500C>A (p.Thr167Lys)

dbSNP: rs1408325840
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Institute of Human Genetics, University of Leipzig Medical Center RCV001253015 SCV001428516 likely pathogenic Adult hypophosphatasia 2018-08-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV005094212 SCV005732260 likely pathogenic not provided 2025-01-15 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with lysine, which is basic and polar, at codon 167 of the ALPL protein (p.Thr167Lys). This variant is not present in population databases (gnomAD no frequency). 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: 975889). 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%. This variant disrupts the p.Thr167 amino acid residue in ALPL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 16583935, 25731960; internal data). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. 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.

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