This sequence change creates a premature translational stop signal (p.Glu370Asnfs*5) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis (PMID: 11283794, 20079931, 24997176, 30202406). This variant is also known as Lys342(1-bp del). ClinVar contains an entry for this variant (Variation ID: 99809). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
ClinVar Genomic variation as it relates to human health
NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Pathogenic
11 out of 16 submissions contributed to this classification
Help
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.
16
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_020366.4(RPGRIP1):c.1107del (p.Glu370fs)
Variation ID: 99809 Accession: VCV000099809.28
- Type and length
-
Deletion, 1 bp
- Location
-
Cytogenetic: 14q11.2 14: 21312458 (GRCh38) [ NCBI UCSC ] 14: 21780617 (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 Feb 20, 2014 Sep 6, 2025 Oct 4, 2024 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_020366.4:c.1107del MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_065099.3:p.Glu370fs frameshift NM_020366.4:c.1107delA MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
frameshift NM_020366.3:c.1103delA NM_020366.3:c.1107delA NC_000014.9:g.21312462del NC_000014.8:g.21780621del NG_008933.1:g.29486del - Protein change
- E370fs
- Other names
-
p.Glu370AsnfsTer5
- Canonical SPDI
- NC_000014.9:21312457:AAAAA:AAAA
-
Global minor allele
frequency (GMAF) HelpThe 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.
- -
- Links
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 | ||
|---|---|---|---|---|---|---|
| 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 |
1130 | 1185 | |
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. |
|---|---|---|---|---|
| Pathogenic (2) |
criteria provided, single submitter
|
Feb 3, 2021 | RCV000086238.9 | |
| Pathogenic (10) |
criteria provided, multiple submitters, no conflicts
|
Mar 26, 2024 | RCV000171128.24 | |
| Pathogenic (1) |
criteria provided, single submitter
|
Aug 27, 2024 | RCV001047199.7 | |
| Pathogenic (1) |
no assertion criteria provided
|
Dec 13, 2017 | RCV000786015.1 | |
| Pathogenic (2) |
criteria provided, multiple submitters, no conflicts
|
Oct 4, 2024 | RCV001800395.5 |
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
(-)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Leber congenital amaurosis 6 |
CENTOGENE GmbH and LLC - Guiding Precision Medicine
Accession: SCV001426643.1
First in ClinVar: Aug 09, 2020 Last updated: Aug 09, 2020 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Nov 07, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Leber congenital amaurosis 6 |
Genome-Nilou Lab
Accession: SCV002044747.1
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
|
Cone-rod dystrophy 13 |
Genome-Nilou Lab
Accession: SCV002044758.1
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
(Mar 26, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Leber congenital amaurosis 6 |
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre
Accession: SCV004806819.1
First in ClinVar: Apr 06, 2024 Last updated: Apr 06, 2024 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Aug 27, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
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: SCV001211139.6
First in ClinVar: Apr 15, 2020 Last updated: Mar 04, 2025 |
Comment:
show
This sequence change creates a premature translational stop signal (p.Glu370Asnfs*5) 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 not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Leber congenital amaurosis (PMID: 11283794, 20079931, 24997176, 30202406). This variant is also known as Lys342(1-bp del). ClinVar contains an entry for this variant (Variation ID: 99809). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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
|
|
|
Pathogenic
(Jun 23, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Leber congenital amaurosis 6 |
DBGen Ocular Genomics
Accession: SCV001815997.2
First in ClinVar: Sep 08, 2021 Last updated: Apr 13, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Number of individuals with the variant: 1
Sex: female
Ethnicity/Population group: unspecified
Geographic origin: Middle East
|
|
|
Pathogenic
(Nov 22, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Leber congenital amaurosis 6 |
3billion
Accession: SCV002058264.3
First in ClinVar: Jan 15, 2022 Last updated: Jun 29, 2025 |
Comment:
show
The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000099809 /PMID: 11283794 /3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Platform type: exome sequencing
|
|
|
Pathogenic
(Feb 03, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Revvity Omics, Revvity
Accession: SCV002019890.4
First in ClinVar: Nov 29, 2021 Last updated: Sep 06, 2025 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Pathogenic
(Apr 07, 2020)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Leber congenital amaurosis 6 |
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital
Accession: SCV001984513.1
First in ClinVar: Oct 30, 2021 Last updated: Oct 30, 2021
Comment:
The p.Glu370fs variant in RPGRIP1 has been previously reported in at least one individual with congenital leber amaurosis (PMIDs: 11283794) but was absent from large … (more)
The p.Glu370fs variant in RPGRIP1 has been previously reported in at least one individual with congenital leber amaurosis (PMIDs: 11283794) but was absent from large population studies such as the Genome Aggregation Database (gnomAD) and the Greater Middle East (GME) Variome Database. This frameshift variant affecting the only known RPGRIP1 transcript is predicted to alter the protein's amino acid sequence beginning at position 370 and lead to a premature termination codon 5 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary this variant meets our criteria for pathogenicity. (less)
|
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Feb 13, 2021)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Leber congenital amaurosis 6 |
Breakthrough Genomics, Breakthrough Genomics
Accession: SCV005088877.2
First in ClinVar: Aug 04, 2024 Last updated: Aug 25, 2024 |
Comment:
show
This variant has been observed in homozygous state in multiple individuals with a clinical diagnosis of Leber congenital amaurosis [PMID: 30202406, 20079931, 24997176] and it was previously reported as recurrent variant (represented as c.1007delA (p.Glu370Asnfs*5) in the article [PMID: 24997176]. (less)
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(Oct 04, 2024)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Cone-rod dystrophy 13 |
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital
Accession: SCV002818118.2
First in ClinVar: Jan 07, 2023 Last updated: Dec 07, 2024 |
Observation: 1
Collection method: research
Allele origin: germline
Affected status: yes
Observation 1
Collection method: research
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(May 01, 2001)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
LEBER CONGENITAL AMAUROSIS 6 |
OMIM
Accession: SCV000025451.2
First in ClinVar: Apr 04, 2013 Last updated: May 23, 2015 |
Observation: 1
Collection method: literature only
Allele origin: germline
Affected status: not provided
Observation 1
Collection method: literature only
Allele origin: germline
Affected status: not provided
Comment on evidence:
In a patient with Leber congenital amaurosis-6 (LCA6; 613826), Dryja et al. (2001) identified homozygosity for a frameshift mutation in the RPGRIP1 gene. The mutation … (more)
In a patient with Leber congenital amaurosis-6 (LCA6; 613826), Dryja et al. (2001) identified homozygosity for a frameshift mutation in the RPGRIP1 gene. The mutation consisted of a 1-bp deletion (A) at codon lys342. (less)
|
|
|
Pathogenic
(Dec 13, 2017)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Leber congenital amaurosis |
Molecular Genetics Laboratory, Institute for Ophthalmic Research
Accession: SCV000924655.1
First in ClinVar: Jun 28, 2019 Last updated: Jun 28, 2019 |
Observation: 1
Collection method: research
Allele origin: inherited
Affected status: yes
Observation 1
Collection method: research
Allele origin: inherited
Affected status: yes
|
|
|
Pathogenic
(Sep 26, 2019)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Leber congenital amaurosis 6 |
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City
Accession: SCV001133096.1
First in ClinVar: Jan 04, 2020 Last updated: Jan 04, 2020 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Pathogenic
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Leber congenital amaurosis 6 |
Laboratory of Genetics in Ophthalmology, Institut Imagine
Accession: SCV001438576.1
First in ClinVar: Oct 23, 2020 Last updated: Oct 23, 2020 |
Observation 1
Collection method: research
Allele origin: inherited
Affected status: yes
Number of individuals with the variant: 1
|
|
|
not provided
(-)
N
Not contributing to aggregate classification
|
no classification provided
|
not provided |
Retina International
Accession: SCV000118384.1
First in ClinVar: Feb 20, 2014 Last updated: Feb 20, 2014
Comment:
http://phencode.bx.psu.edu/cgi-bin/phencode/phencode?build=hg19&id=RISN_RPGRIP:c.1103delA
|
Observation: 1
Collection method: not provided
Allele origin: not provided
Affected status: not provided
Observation 1
Collection method: not provided
Allele origin: not provided
Affected status: not provided
|
|
Comment:
Comment:
The variant is not observed in the gnomAD v2.1.1 dataset. Predicted Consequence/Location: Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. The variant has been reported at least twice as pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000099809 /PMID: 11283794 /3billion dataset). Therefore, this variant is classified as Pathogenic according to the recommendation of ACMG/AMP guideline.
Comment:
This variant has been observed in homozygous state in multiple individuals with a clinical diagnosis of Leber congenital amaurosis [PMID: 30202406, 20079931, 24997176] and it was previously reported as recurrent variant (represented as c.1007delA (p.Glu370Asnfs*5) in the article [PMID: 24997176].
Comment:
PVS1, PM2, PP4
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Successful application of genome sequencing in a diagnostic setting: 1007 index cases from a clinically heterogeneous cohort. | Bertoli-Avella AM | European journal of human genetics : EJHG | 2021 | PMID: 32860008 |
| Applying filtration steps to interpret the results of whole-exome sequencing in a consanguineous population to achieve a high detection rate. | Alfares AA | International journal of health sciences | 2018 | PMID: 30202406 |
| Genetic analysis of strictly defined Leber congenital amaurosis with (and without) neurodevelopmental delay. | Khan AO | The British journal of ophthalmology | 2014 | PMID: 24997176 |
| Autozygome-guided exome sequencing in retinal dystrophy patients reveals pathogenetic mutations and novel candidate disease genes. | Abu-Safieh L | Genome research | 2013 | PMID: 23105016 |
| Visual acuity in patients with Leber's congenital amaurosis and early childhood-onset retinitis pigmentosa. | Walia S | Ophthalmology | 2010 | PMID: 20079931 |
| 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 |
| Null RPGRIP1 alleles in patients with Leber congenital amaurosis. | Dryja TP | American journal of human genetics | 2001 | PMID: 11283794 |
Text-mined citations for rs61751266 ...
HelpThese 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 Sep 14, 2025
This date represents the last time this VCV record was updated. The update may be due to an update to one of the included submitted records (SCVs), or due to an update that ClinVar made to the variant such as adding HGVS expressions or a rs number. So this date may be different from the date of the “most recent submission” reported at the top of this page.