ClinVar Miner

Submissions for variant NM_000478.6(ALPL):c.980T>G (p.Phe327Cys)

dbSNP: rs779832611
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001972665 SCV002247263 pathogenic not provided 2023-10-30 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine, which is neutral and non-polar, with cysteine, which is neutral and slightly polar, at codon 327 of the ALPL protein (p.Phe327Cys). This variant is present in population databases (rs779832611, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of hypophosphatasia (Invitae). This variant is also known as F310C. ClinVar contains an entry for this variant (Variation ID: 1457572). 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 with a positive predictive value of 95%. This variant disrupts the p.Phe327 amino acid residue in ALPL. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 8954059, 9814472, 12412800, 15660230). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002276955 SCV002564894 likely pathogenic Osteogenesis imperfecta 2022-06-14 criteria provided, single submitter clinical testing
Baylor Genetics RCV003475237 SCV004195008 likely pathogenic Adult hypophosphatasia 2023-07-07 criteria provided, single submitter clinical testing

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