VCV002737218.4 - ClinVar

NM_006915.3(RP2):c.632G>A (p.Arg211His)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance (1); Likely benign (1)

2 out of 2 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_006915.3(RP2):c.632G>A (p.Arg211His)

Variation ID: 2737218 Accession: VCV002737218.4

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: Xp11.3 X: 46713440 (GRCh37) [ NCBI UCSC ] X: 46854005 (GRCh38) [ 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 14, 2024	Feb 23, 2026	Jan 1, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_006915.3:c.632G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_008846.2:p.Arg211His	missense
NC_000023.11:g.46854005G>A
NC_000023.10:g.46713440G>A
NG_009107.1:g.22094G>A

Protein change

R211H

Other names

Canonical SPDI

NC_000023.11:46854004: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.

Exome Aggregation Consortium (ExAC) 0.00001

The Genome Aggregation Database (gnomAD) 0.00001

Trans-Omics for Precision Medicine (TOPMed) 0.00002

The Genome Aggregation Database (gnomAD), exomes 0.00001

Links

ClinGen: CA10394228 dbSNP: rs782164955 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.
RP2		Sufficient evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	471	693

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	Likely benign (1)	criteria provided, single submitter	Jan 1, 2026	RCV003560239.4
not specified	Uncertain significance (1)	criteria provided, single submitter	Nov 6, 2024	RCV005063027.1

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.
Uncertain significance (Nov 06, 2024) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not specified	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV005727014.1 First in ClinVar: Feb 16, 2025 Last updated: Feb 16, 2025	Publications: PubMed (2) PubMed: 16969763‚ 28209709 Comment: show Variant summary: RP2 c.632G>A (p.Arg211His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 183390 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.632G>A has been reported in the literature in one individual affected with distinct retinal dystrophies, without primary information (Pelletier_2007). These report(s) do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa, X-Linked. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Liu_2017). The following publications have been ascertained in the context of this evaluation (PMID: 28209709, 16969763). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as 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

Likely benign (Jan 01, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV004300004.3 First in ClinVar: Feb 14, 2024 Last updated: Feb 23, 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

Comment:

Variant summary: RP2 c.632G>A (p.Arg211His) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 183390 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.632G>A has been reported in the literature in one individual affected with distinct retinal dystrophies, without primary information (Pelletier_2007). These report(s) do not provide unequivocal conclusions about association of the variant with Retinitis Pigmentosa, X-Linked. At least one publication reports experimental evidence evaluating an impact on protein function. These results showed no damaging effect of this variant (Liu_2017). The following publications have been ascertained in the context of this evaluation (PMID: 28209709, 16969763). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as uncertain significance.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Pathogenic mutations in retinitis pigmentosa 2 predominantly result in loss of RP2 protein stability in humans and zebrafish.	Liu F	The Journal of biological chemistry	2017	PMID: 28209709
Comprehensive survey of mutations in RP2 and RPGR in patients affected with distinct retinal dystrophies: genotype-phenotype correlations and impact on genetic counseling.	Pelletier V	Human mutation	2007	PMID: 16969763

Text-mined citations for rs782164955 ...

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 Mar 01, 2026