This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
NM_000350.3(ABCA4):c.3602T>G (p.Leu1201Arg)
Germline
Classification
Help
criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.
Benign/Likely benign
Benign (4); Likely benign (3)
Benign (4); Likely benign (3)
7 out of 13 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.
13
Somatic
No data submitted for somatic clinical impact
Somatic
No data submitted for oncogenicity
Variant Details
- Identifiers
-
NM_000350.3(ABCA4):c.3602T>G (p.Leu1201Arg)
Variation ID: 7903 Accession: VCV000007903.31
- Type and length
-
single nucleotide variant, 1 bp
- Location
-
Cytogenetic: 1p22.1 1: 94040048 (GRCh38) [ NCBI UCSC ] 1: 94505604 (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 Apr 4, 2013 Mar 7, 2026 Feb 1, 2026 - HGVS
-
... more HGVS ... less HGVSNucleotide Protein Molecular
consequenceNM_000350.3:c.3602T>G MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.
NP_000341.2:p.Leu1201Arg missense NM_001425324.1:c.3380T>G NP_001412253.1:p.Leu1127Arg missense NC_000001.11:g.94040048A>C NC_000001.10:g.94505604A>C NG_009073.1:g.86102T>G NG_009073.2:g.86100T>G P78363:p.Leu1201Arg - Protein change
- L1201R, L1127R
- Other names
- -
- Canonical SPDI
- NC_000001.11:94040047:A:C
-
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.
-
0.02915 (C)
-
Allele frequency
Help
The frequency of the allele represented by this VCV record.
-
The Genome Aggregation Database (gnomAD), exomes 0.00258
The Genome Aggregation Database (gnomAD), exomes 0.00667
Exome Aggregation Consortium (ExAC) 0.01364
The Genome Aggregation Database (gnomAD) 0.02687
The Genome Aggregation Database (gnomAD) 0.02895
1000 Genomes Project 0.02915
Trans-Omics for Precision Medicine (TOPMed) 0.02942
1000 Genomes Project 30x 0.02983
- 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. |
|||
| ABCA4 | - | - |
GRCh38 GRCh37 |
4241 | 4655 | |
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. |
|---|---|---|---|---|
| no classifications from unflagged records (1) |
no classifications from unflagged records
|
Nov 2, 2023 | RCV000008361.11 | |
| Benign (5) |
criteria provided, multiple submitters, no conflicts
|
Feb 1, 2026 | RCV000085583.25 | |
| Benign (3) |
criteria provided, single submitter
|
Mar 5, 2015 | RCV000176456.16 | |
| Likely benign (2) |
criteria provided, single submitter
|
May 28, 2019 | RCV000408567.15 | |
| Likely benign (1) |
criteria provided, single submitter
|
Apr 27, 2017 | RCV001096421.12 | |
| Likely benign (1) |
criteria provided, single submitter
|
Jan 1, 2023 | RCV004814861.1 |
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. |
|
|---|---|---|---|---|---|
|
Likely benign
(May 28, 2019)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Severe early-childhood-onset retinal dystrophy |
Mendelics
Accession: SCV001135348.1
First in ClinVar: Jan 09, 2020 Last updated: Jan 09, 2020 |
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: unknown
|
|
|
Likely benign
(Apr 27, 2017)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
ABCA4-Related Disorders |
Illumina Laboratory Services, Illumina
Accession: SCV001252629.1
First in ClinVar: May 31, 2020 Last updated: May 31, 2020 |
Comment:
show
This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. (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
|
|
|
Benign
(Mar 05, 2015)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not specified |
Eurofins Ntd Llc (ga)
Accession: SCV000228115.6
First in ClinVar: Jun 28, 2015 Last updated: Apr 13, 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
Number of individuals with the variant: 1
Zygosity: 1 Single Heterozygote
Sex: mixed
|
|
|
Benign
(Feb 01, 2026)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
Labcorp Genetics (formerly Invitae), Labcorp
Accession: SCV001729889.6
First in ClinVar: Jun 15, 2021 Last updated: Mar 07, 2026 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: unknown
|
|
|
Benign
(Mar 03, 2015)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
GeneDx
Accession: SCV001880968.1
First in ClinVar: Sep 19, 2021 Last updated: Sep 19, 2021 |
Comment:
show
This variant is associated with the following publications: (PMID: 28559085, 20647261, 29925512, 25066811, 24011517, 23982839, 27884173, 9973280, 25097241, 16123440, 19074458, 20981092) (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
|
|
|
Benign
(Sep 21, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
not provided |
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories
Accession: SCV002047732.2
First in ClinVar: Jan 08, 2022 Last updated: Feb 20, 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
|
|
|
Likely benign
(Jan 01, 2023)
C
Contributing to aggregate classification
|
criteria provided, single submitter
|
Retinal dystrophy |
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg
Accession: SCV000281871.3
First in ClinVar: Dec 07, 2016 Last updated: Dec 28, 2024 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Likely benign
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not provided |
Clinical Genetics, Academic Medical Center
Study: VKGL Data-share Consensus
Accession: SCV001925438.1 First in ClinVar: Sep 24, 2021 Last updated: Sep 24, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Benign
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not specified |
Department of Pathology and Laboratory Medicine, Sinai Health System
Additional submitter:
Franklin by Genoox
Study: The Canadian Open Genetics Repository (COGR)
Accession: SCV001553447.1 First in ClinVar: Apr 13, 2021 Last updated: Apr 13, 2021 |
Comment:
show
The ABCA4 p.Leu1201Arg variant was identified in 19 of 988 proband chromosomes (frequency: 0.019) from individuals or families with Stargardt disease and cone-rod dystrophy (Schulz_2017_PMID:28118664; Utz_2013_PMID:24011517; Zernant_2014_PMID:25066811; Fishman_2003_PMID:12796258). The variant was identified in dbSNP (ID: rs61750126), ClinVar (classified as benign by EGL Genetics, likely benign by Illumina and likely pathogenic by Institute of Human Genetics, Univ. Regensburg) and LOVD 3.0 (classified as a VUS and likely benign). The variant was also identified in control databases in 2402 of 266312 chromosomes (114 homozygous) at a frequency of 0.009019 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2219 of 23326 chromosomes (freq: 0.09513), Other in 32 of 6916 chromosomes (freq: 0.004627), Latino in 133 of 34270 chromosomes (freq: 0.003881), European (non-Finnish) in 16 of 120738 chromosomes (freq: 0.000133) and South Asian in 2 of 28188 chromosomes (freq: 0.000071), while the variant was not observed in the Ashkenazi Jewish, East Asian or European (Finnish) populations. The p.Leu1201 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. (less)
Observation: 1
Collection method: clinical testing
Allele origin: unknown
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: unknown
Affected status: yes
|
|
|
Benign
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
not specified |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+
Study: VKGL Data-share Consensus
Accession: SCV001951648.1 First in ClinVar: Oct 02, 2021 Last updated: Oct 02, 2021 |
Observation: 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
Observation 1
Collection method: clinical testing
Allele origin: germline
Affected status: yes
|
|
|
Benign
(-)
N
Not contributing to aggregate classification
|
no assertion criteria provided
|
Severe early-childhood-onset retinal dystrophy
(Autosomal recessive inheritance)
|
Ophthalmo-Genetics Lab, Instituto de Oftalmologia Conde de Valenciana
Accession: SCV005047006.1
First in ClinVar: Jun 09, 2024 Last updated: Jun 09, 2024 |
Observation: 1
Collection method: research
Allele origin: germline
Affected status: yes
Observation 1
Collection method: research
Allele origin: germline
Affected status: yes
|
|
|
not provided
(-)
N
Not contributing to aggregate classification
|
no classification provided
|
not provided |
Retina International
Accession: SCV000117721.1
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_ABCR:c.3602T>G
|
Observation: 1
Collection method: not provided
Allele origin: unknown
Affected status: not provided
Observation 1
Collection method: not provided
Allele origin: unknown
Affected status: not provided
|
|
|
Pathogenic
(Jun 01, 2003)
N
Not contributing to aggregate classification
|
Flagged submission
flagged submission
Reason: Outlier claim with insufficient supporting evidence
Source: ClinGen
|
CONE-ROD DYSTROPHY 3 |
OMIM
Accession: SCV000028569.1
First in ClinVar: Apr 04, 2013 Last updated: Apr 04, 2013 |
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 2 patients with cone-rod dystrophy (CORD3; 604116) with comparatively mild funduscopically apparent pigmentary changes, Fishman et al. (2003) identified a heterozygous leu1201-to-arg mutation (L1201R) … (more)
In 2 patients with cone-rod dystrophy (CORD3; 604116) with comparatively mild funduscopically apparent pigmentary changes, Fishman et al. (2003) identified a heterozygous leu1201-to-arg mutation (L1201R) in the ABCA4 gene. (less)
|
|
| Flagged submissions do not contribute to the aggregate classification or review status for the variant. Learn more | |||||
Comment:
Comment:
This variant is associated with the following publications: (PMID: 28559085, 20647261, 29925512, 25066811, 24011517, 23982839, 27884173, 9973280, 25097241, 16123440, 19074458, 20981092)
Comment:
The ABCA4 p.Leu1201Arg variant was identified in 19 of 988 proband chromosomes (frequency: 0.019) from individuals or families with Stargardt disease and cone-rod dystrophy (Schulz_2017_PMID:28118664; Utz_2013_PMID:24011517; Zernant_2014_PMID:25066811; Fishman_2003_PMID:12796258). The variant was identified in dbSNP (ID: rs61750126), ClinVar (classified as benign by EGL Genetics, likely benign by Illumina and likely pathogenic by Institute of Human Genetics, Univ. Regensburg) and LOVD 3.0 (classified as a VUS and likely benign). The variant was also identified in control databases in 2402 of 266312 chromosomes (114 homozygous) at a frequency of 0.009019 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: African in 2219 of 23326 chromosomes (freq: 0.09513), Other in 32 of 6916 chromosomes (freq: 0.004627), Latino in 133 of 34270 chromosomes (freq: 0.003881), European (non-Finnish) in 16 of 120738 chromosomes (freq: 0.000133) and South Asian in 2 of 28188 chromosomes (freq: 0.000071), while the variant was not observed in the Ashkenazi Jewish, East Asian or European (Finnish) populations. The p.Leu1201 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign.
Citations for germline classification of this variant
Help| Title | Author | Journal | Year | Link |
|---|---|---|---|---|
| Mutation Spectrum of the ABCA4 Gene in 335 Stargardt Disease Patients From a Multicenter German Cohort-Impact of Selected Deep Intronic Variants and Common SNPs. | Schulz HL | Investigative ophthalmology & visual science | 2017 | PMID: 28118664 |
| Genetic and clinical analysis of ABCA4-associated disease in African American patients. | Zernant J | Human mutation | 2014 | PMID: 25066811 |
| Identification of three ABCA4 sequence variations exclusive to African American patients in a cohort of patients with Stargardt disease. | Utz VM | American journal of ophthalmology | 2013 | PMID: 24011517 |
| ABCA4 gene screening by next-generation sequencing in a British cohort. | Fujinami K | Investigative ophthalmology & visual science | 2013 | PMID: 23982839 |
| ABCA4 gene sequence variations in patients with autosomal recessive cone-rod dystrophy. | Fishman GA | Archives of ophthalmology (Chicago, Ill. : 1960) | 2003 | PMID: 12796258 |
| http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=ABCA4 | - | - | - | - |
Text-mined citations for rs61750126 ...
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 Apr 13, 2026
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.