VCV001367498.8 - ClinVar

NM_020806.5(GPHN):c.2123G>A (p.Arg708Gln)

Germline

Classification

criteria provided, single submitter. Learn more about how ClinVar calculates review status.

Uncertain significance
Uncertain significance (1)

This classification is based on the single submission received

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_020806.5(GPHN):c.2123G>A (p.Arg708Gln)

Variation ID: 1367498 Accession: VCV001367498.8

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q23.3 14: 67179621 (GRCh38) [ NCBI UCSC ] 14: 67646338 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Mar 28, 2022	Feb 15, 2026	Oct 13, 2023

HGVS

Nucleotide	Protein	Molecular consequence
NM_020806.5:c.2123G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_065857.1:p.Arg708Gln	missense
NM_001024218.2:c.2024G>A	NP_001019389.1:p.Arg675Gln	missense
NM_001377514.1:c.2183G>A	NP_001364443.1:p.Arg728Gln	missense
NM_001377515.1:c.2153G>A	NP_001364444.1:p.Arg718Gln	missense
NM_001377516.1:c.2144G>A	NP_001364445.1:p.Arg715Gln	missense
NM_001377517.1:c.2096G>A	NP_001364446.1:p.Arg699Gln	missense
NM_001377518.1:c.2081G>A	NP_001364447.1:p.Arg694Gln	missense
NM_001377519.1:c.2063G>A	NP_001364448.1:p.Arg688Gln	missense
NC_000014.9:g.67179621G>A
NC_000014.8:g.67646338G>A
NG_008875.1:g.677214G>A

... more HGVS ... less HGVS

Protein change

R675Q, R718Q, R728Q, R688Q, R694Q, R699Q, R708Q, R715Q

Other names

Canonical SPDI

NC_000014.9:67179620:G:A

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

Links

ClinGen: CA262756292 dbSNP: rs867353439 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
GPHN		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	937	2684

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C	Uncertain significance (1)	criteria provided, single submitter	Oct 13, 2023	RCV001947319.8

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Uncertain significance (Oct 13, 2023) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Sulfite oxidase deficiency due to molybdenum cofactor deficiency type C	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002133762.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 15, 2026	Comment: show This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 708 of the GPHN protein (p.Arg708Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GPHN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1367498). 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 GPHN 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. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 708 of the GPHN protein (p.Arg708Gln). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with GPHN-related conditions. ClinVar contains an entry for this variant (Variation ID: 1367498). 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 GPHN 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.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs867353439 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Feb 15, 2026