ClinVar Miner

Submissions for variant NM_000187.4(HGD):c.125A>C (p.Glu42Ala)

gnomAD frequency: 0.00007  dbSNP: rs373921680
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001384280 SCV001583721 pathogenic Alkaptonuria 2023-06-25 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. 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 HGD protein function. ClinVar contains an entry for this variant (Variation ID: 1071746). This missense change has been observed in individuals with alkaptonuria (PMID: 9529363, 25681086). This variant is present in population databases (rs373921680, gnomAD 0.009%). This sequence change replaces glutamic acid, which is acidic and polar, with alanine, which is neutral and non-polar, at codon 42 of the HGD protein (p.Glu42Ala).
Fulgent Genetics, Fulgent Genetics RCV001384280 SCV002792806 likely pathogenic Alkaptonuria 2022-03-15 criteria provided, single submitter clinical testing
Department Of Human Genetics, Institute Of Clinical And Translational Research, Biomedical Research Center, Slovak Academy Of Sciences RCV001384280 SCV004098948 pathogenic Alkaptonuria no assertion criteria provided research The variant was originally described in AKU patient in PMID:9529363. It has been submitted to the HGD gene mutation database (, DB-ID: AKU_00008).

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.