VCV001216773.21 - ClinVar

NM_001854.4(COL11A1):c.2513G>A (p.Gly838Glu)

Germline

Classification

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

Pathogenic/Likely pathogenic
Pathogenic (1); Likely pathogenic (1)

2 out of 4 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_001854.4(COL11A1):c.2513G>A (p.Gly838Glu)

Variation ID: 1216773 Accession: VCV001216773.21

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1p21.1 1: 102984181 (GRCh38) [ NCBI UCSC ] 1: 103449737 (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	Sep 8, 2021	Feb 15, 2026	Dec 24, 2025

HGVS

Nucleotide	Protein	Molecular consequence
NM_001854.4:c.2513G>A MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001845.3:p.Gly838Glu	missense
NM_001190709.2:c.2396G>A	NP_001177638.1:p.Gly799Glu	missense
NM_080629.3:c.2549G>A	NP_542196.2:p.Gly850Glu	missense
NM_080630.4:c.2165G>A	NP_542197.3:p.Gly722Glu	missense
NR_134980.2:n.2857G>A		non-coding transcript variant
NC_000001.11:g.102984181C>T
NC_000001.10:g.103449737C>T
NG_008033.2:g.129316G>A

... more HGVS ... less HGVS

Protein change

G722E, G799E, G838E, G850E

Other names

Canonical SPDI

NC_000001.11:102984180:C:T

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) 0.00001

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00008

Links

ClinGen: CA27704961 dbSNP: rs372419698 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.
COL11A1		Little evidence for dosage pathogenicity	No evidence available	GRCh38 GRCh37	3389	3513

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/Likely pathogenic (2)	criteria provided, multiple submitters, no conflicts	Dec 24, 2025	RCV001587154.17
Fibrochondrogenesis 1 Hearing loss, autosomal dominant 37 Marshall syndrome Stickler syndrome type 2	not provided (1)	no classification provided	-	RCV001825009.3
Stickler syndrome type 2	Likely pathogenic (1)	no assertion criteria provided	Sep 25, 2024	RCV004770182.1

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 pathogenic (Oct 01, 2025) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001820835.9 First in ClinVar: Sep 08, 2021 Last updated: Oct 12, 2025	Comment: show Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25240749) (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 (Dec 24, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV002277126.5 First in ClinVar: Mar 28, 2022 Last updated: Feb 15, 2026	Comment: show This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 838 of the COL11A1 protein (p.Gly838Glu). This variant is present in population databases (rs372419698, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal dominant Stickler syndrome (internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1216773). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt COL11A1 protein function with a positive predictive value of 80%. 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

Likely pathogenic (Sep 25, 2024) N Not contributing to aggregate classification	no assertion criteria provided	Stickler syndrome type 2	Autoinflammatory diseases unit, CHU de Montpellier Accession: SCV005381979.1 First in ClinVar: Oct 26, 2024 Last updated: Oct 26, 2024	Observation: 1 Collection method: clinical testing Allele origin: unknown Affected status: yes Observation 1 Collection method: clinical testing Allele origin: unknown Affected status: yes

not provided (-) N Not contributing to aggregate classification	no classification provided	Stickler syndrome type 2 Marshall syndrome Fibrochondrogenesis 1 Hearing loss, autosomal dominant 37 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.	GenomeConnect, ClinGen Accession: SCV002075112.3 First in ClinVar: Feb 12, 2022 Last updated: Apr 13, 2025	Comment: show Variant interpreted as Likely pathogenic and reported on 06-17-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant. (less) Observation: 1 Collection method: phenotyping only Allele origin: unknown Affected status: unknown more Observation 1 Collection method: phenotyping only Allele origin: unknown Affected status: unknown Clinical Features: Phenotypic abnormality (present) Indication for testing: Diagnostic Age: 30-39 years Sex: female Platform type: Gene Panel Sequencing Method: Sanger Sequencing Testing laboratory: GeneDx Date variant was reported to submitter: 2020-06-17 Testing laboratory interpretation: Likely pathogenic

Comment:

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 25240749)

Comment:

This sequence change replaces glycine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 838 of the COL11A1 protein (p.Gly838Glu). This variant is present in population databases (rs372419698, gnomAD 0.007%). This missense change has been observed in individual(s) with autosomal dominant Stickler syndrome (internal data). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1216773). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt COL11A1 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.

Comment:

Variant interpreted as Likely pathogenic and reported on 06-17-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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 rs372419698 ...

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