VCV000095949.12 - ClinVar

NM_020366.4(RPGRIP1):c.2775G>A (p.Trp925Ter)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Pathogenic
Pathogenic (5)

5 out of 5 submissions contributed to this classification

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_020366.4(RPGRIP1):c.2775G>A (p.Trp925Ter)

Variation ID: 95949 Accession: VCV000095949.12

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q11.2 14: 21327687 (GRCh38) [ NCBI UCSC ] 14: 21795846 (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	Jun 29, 2015	Feb 23, 2026	Jun 20, 2022

HGVS

Nucleotide	Protein	Molecular consequence
NM_020366.4:c.2775G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_065099.3:p.Trp925Ter	nonsense
NM_001377523.1:c.753G>A	NP_001364452.1:p.Trp251Ter	nonsense
NM_001377948.1:c.1701G>A	NP_001364877.1:p.Trp567Ter	nonsense
NM_001377949.1:c.861G>A	NP_001364878.1:p.Trp287Ter	nonsense
NM_001377950.1:c.753G>A	NP_001364879.1:p.Trp251Ter	nonsense
NM_001377951.1:c.255G>A	NP_001364880.1:p.Trp85Ter	nonsense
NC_000014.9:g.21327687G>A
NC_000014.8:g.21795846G>A
NG_008933.1:g.44711G>A

... more HGVS ... less HGVS

Protein change

W925*, W251*, W287*, W567*, W85*

Other names

Canonical SPDI

NC_000014.9:21327686: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 0.00000

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD), exomes 0.00001

Links

ClinGen: CA223564 dbSNP: rs398124354 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.
RPGRIP1		Gene associated with autosomal recessive phenotype	No evidence available	GRCh38 GRCh37	1200	1255

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.
not provided	Pathogenic (1)	criteria provided, single submitter	Oct 24, 2013	RCV000082001.8
Leber congenital amaurosis	Pathogenic (1)	criteria provided, single submitter	Apr 13, 2018	RCV000710048.2
Cone-rod dystrophy 13	Pathogenic (1)	criteria provided, single submitter	Nov 7, 2021	RCV001800387.2
Leber congenital amaurosis 6	Pathogenic (1)	criteria provided, single submitter	Nov 7, 2021	RCV001800386.2
Cone-rod dystrophy 13 Leber congenital amaurosis 6	Pathogenic (1)	criteria provided, single submitter	Jun 20, 2022	RCV001857395.6

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.
Pathogenic (Oct 24, 2013) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not provided	Eurofins Ntd Llc (ga) Accession: SCV000113936.9 First in ClinVar: Jan 17, 2014 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RPGRIP1 Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 1 Zygosity: 1 Single Heterozygote Sex: mixed

Pathogenic (Nov 07, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Leber congenital amaurosis 6	Genome-Nilou Lab Accession: SCV002045231.1 First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Pathogenic (Nov 07, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Cone-rod dystrophy 13	Genome-Nilou Lab Accession: SCV002045242.1 First in ClinVar: Jan 03, 2022 Last updated: Jan 03, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no

Pathogenic (Apr 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Leber congenital amaurosis	Center of Genomic medicine, Geneva, University Hospital of Geneva Accession: SCV000840426.2 First in ClinVar: Oct 19, 2018 Last updated: Apr 13, 2025	Comment: show This variant was identified in combination with another variant in the same gene (compound heterozygosity) in patient with Leber congenital amaurosis. (less) Observation: 1 Collection method: clinical testing Allele origin: paternal Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: paternal Affected status: yes Number of individuals with the variant: 2 Age: 0-9 years Sex: male

Pathogenic (Jun 20, 2022) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Leber congenital amaurosis 6 Cone-rod dystrophy 13 Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002235173.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 23, 2026	Publications: PubMed (2) PubMed: 11528500‚ 23105016 Comment: show This sequence change creates a premature translational stop signal (p.Trp925*) in the RPGRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPGRIP1 are known to be pathogenic (PMID: 11528500, 23105016). This variant is present in population databases (rs398124354, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RPGRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 95949). For these reasons, this variant has been classified as Pathogenic. (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 creates a premature translational stop signal (p.Trp925*) in the RPGRIP1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in RPGRIP1 are known to be pathogenic (PMID: 11528500, 23105016). This variant is present in population databases (rs398124354, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with RPGRIP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 95949). For these reasons, this variant has been classified as Pathogenic.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes.	Abu-Safieh L	Genome research	2013	PMID: 23105016
Complete exon-intron structure of the RPGR-interacting protein (RPGRIP1) gene allows the identification of mutations underlying Leber congenital amaurosis.	Gerber S	European journal of human genetics : EJHG	2001	PMID: 11528500
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=RPGRIP1	-	-	-	-

Text-mined citations for rs398124354 ...

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 Apr 13, 2026