# NM_001920.5(DCN):c.941del (p.Pro314fs)

https://sugi.bio/variant/dcn-p-pro314fs

## Summary

**DCN p.Pro314fs (c.941del)** is classified **Pathogenic** in DCN (ClinVar, No assertion criteria, 2 submitters; last evaluated 2011-12-01). No gnomAD frequency available for this variant; Associated with congenital stromal corneal dystrophy.

**At a glance:** Pathogenic · review: No assertion criteria · rsID rs80338742 · 2 submitters · 1 linked condition · no gnomAD frequency available for this variant

## For patients & families {#patients}

This is a change in the DCN gene that is reported as disease-causing, but on limited review, submitted by 2 submitters, and is linked to congenital stromal corneal dystrophy.

*Reference information, not medical advice, and not a prediction for any individual. A genetic counselor or clinician can interpret what it means for you and your family.*

|  |  |
| --- | --- |
| Typical inheritance (of this condition) | Autosomal dominant |
| Age of onset (of this condition) | Neonatal |
| Diagnostic panels | DCN is a diagnostic-grade gene on 2 Genomics England panels |

**Support & next steps:** [Condition overview & support (NIH GARD)](https://rarediseases.info.nih.gov/diseases/0016943/index) · [Find a genetic counselor (NSGC)](https://findageneticcounselor.nsgc.org/).

## Identity {#identity}

| Field | Value |
| --- | --- |
| Gene | [DCN](https://sugi.bio/atlas/gene/DCN/) |
| Protein change (HGVS p.) | p.Pro314fs |
| Coding change (HGVS c.) | c.941del |
| MANE Select transcript | [NM_001920](https://www.ncbi.nlm.nih.gov/nuccore/NM_001920) |
| dbSNP | [rs80338742](https://www.ncbi.nlm.nih.gov/snp/rs80338742/) |
| Variant type | Deletion |
| Location | chr12:91146197-91146197 (GRCh38) |
| ClinVar | [VCV21302](https://www.ncbi.nlm.nih.gov/clinvar/variation/21302/) |

**All HGVS expressions:** `NC_000012.11:g.91539976del`, `NC_000012.12:g.91146199del`, `NG_011672.1:g.41833del`, `NM_001920.5:c.941del`, `NM_133503.4:c.941del`, `NM_133504.3:c.614del`, `NM_133505.3:c.500del`, `NM_133506.3:c.380del`, `NM_133507.3:c.*39del`

## Computational & population evidence {#evidence}

**Concordance:** Mixed / partial computational evidence (see below).

- **Missense predictors (AlphaMissense/REVEL/SaProt) do not apply** to this variant type — they score amino-acid substitutions only. For non-missense variants the computational signal comes from conservation (below), not from a missing predictor score.
- Conservation: phyloP -0.656, GERP -2.89, phastCons 0.029 — not a conserved position (phyloP < 0.1, ACGS BP7 cut)
- Molecular consequence: **frameshift** — a predicted loss-of-function variant. Gene population constraint: LOEUF 0.789, pLI 0.1405. *Descriptive; not an applied PVS1 code.*
- Nonsense-mediated decay: the premature termination codon is **in the last exon (8 of 8)** — predicted to **escape NMD**, so the truncated protein is likely expressed. An input to PVS1, not an applied code.
- SpliceAI: **not assessed** — the release is built from a substitutions-only source, so it holds no deletion variants. That is a property of the dataset, not of the variant, and is not evidence against a splicing effect.
- Population frequency: **no gnomAD frequency available for this variant** — rarity (ACMG PM2) and BA1/BS1 cannot be assessed for this variant.

*Computational predictors are not independent (ClinGen Variant Classification guidance): AlphaMissense (Cheng et al. 2023) carries the ACMG weight for missense and conservation (phyloP/GERP/phastCons) for non-missense; REVEL (Pejaver-2022 calibrated strength bands) and SaProt (Su et al. 2023, structure-aware, ClinVar-independent protein language model, raw LLR) are shown as orthogonal agreement signals, not additive. For frequency, the gnomAD v4.1 grpmax filtering allele frequency (FAF95) is ClinGen's designated BA1/BS1 input (gnomAD v4 guidance v3.0, June 2025); BA1/BS1 thresholds are disease-specific, not a blanket 5%. Predictions, not a clinical determination.*

## Gene constraint & dosage {#gene-context}

**DCN** population constraint: LOEUF 0.789, pLI 0.1405, missense-Z 0.79087. *Lower LOEUF and higher pLI indicate a gene that tolerates loss-of-function poorly; ClinGen dosage is the curated haploinsufficiency call.*

## Protein context {#protein}

Residue **314** lies in a disulfide bond.

AlphaFold model confidence (whole protein): pLDDT 88.60, 84% of residues very-high.

## What this gene does {#gene-function}

*Describes the biological roles of DCN (the gene this variant disrupts) — not effects measured for this specific variant. A damaging variant is expected to affect these functions and pathways; the degree depends on the variant.*

**How this variant is thought to act:** DCN's established molecular role includes RNA binding. In Reactome, DCN is annotated in disease pathway(s) including **Defective B3GALT6 causes EDSP2 and SEMDJL1**, **Defective B3GAT3 causes JDSSDHD**.

**Disease mechanism (Reactome):** DCN loss or alteration is curated in [Defective B3GALT6 causes EDSP2 and SEMDJL1](https://reactome.org/content/detail/R-HSA-4420332), [Defective B3GAT3 causes JDSSDHD](https://reactome.org/content/detail/R-HSA-3560801), [Defective B4GALT7 causes EDS, progeroid type](https://reactome.org/content/detail/R-HSA-3560783).

### Pathways affected {#pathways}

DCN participates in **12 Reactome pathways** (⚕ = disease pathway):

| Pathway (Reactome) | Evidence |
| --- | --- |
| ⚕ [Defective B3GALT6 causes EDSP2 and SEMDJL1](https://reactome.org/content/detail/R-HSA-4420332) | curated |
| ⚕ [Defective B3GAT3 causes JDSSDHD](https://reactome.org/content/detail/R-HSA-3560801) | curated |
| ⚕ [Defective B4GALT7 causes EDS, progeroid type](https://reactome.org/content/detail/R-HSA-3560783) | curated |
| ⚕ [Defective CHST14 causes EDS, musculocontractural type](https://reactome.org/content/detail/R-HSA-3595174) | curated |
| ⚕ [Defective CHST3 causes SEDCJD](https://reactome.org/content/detail/R-HSA-3595172) | curated |
| ⚕ [Defective CHSY1 causes TPBS](https://reactome.org/content/detail/R-HSA-3595177) | curated |
| [CS-GAG biosynthesis](https://reactome.org/content/detail/R-HSA-2022870) | curated |
| [CS/DS degradation](https://reactome.org/content/detail/R-HSA-2024101) | curated |
| [DS-GAG biosynthesis](https://reactome.org/content/detail/R-HSA-2022923) | curated |
| [Degradation of the extracellular matrix](https://reactome.org/content/detail/R-HSA-1474228) | curated |
| [Glycosaminoglycan-protein linkage region biosynthesis](https://reactome.org/content/detail/R-HSA-1971475) | curated |
| [ECM proteoglycans](https://reactome.org/content/detail/R-HSA-3000178) | electronic |

### Molecular function & processes (GO — experimentally supported) {#go}

**Molecular function:** RNA binding.

**Biological process:** positive regulation of autophagy, negative regulation of endothelial cell migration, positive regulation of macroautophagy, negative regulation of angiogenesis, positive regulation of transcription by RNA polymerase II, positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction.

## Clinical significance {#significance}

**Pathogenic** — review status No assertion criteria *(no assertion criteria provided)*, last evaluated 2011-12-01.

**Submitter consensus:** conflicting (1 Pathogenic, 1 not provided).

**Submission history:** 2 submissions (2011); classifications have differed over time.

### Submitter classifications {#submitters}

| Submitter | Classification | Review | Method | Date |
| --- | --- | --- | --- | --- |
| OMIM | Pathogenic | no assertion criteria provided | literature only | 2011-12-01 |
| GeneReviews | not provided | no classification provided | literature only |  |

## Associated conditions {#conditions}

[congenital stromal corneal dystrophy](https://sugi.bio/atlas/disease/congenital-stromal-corneal-dystrophy/).

**Reported phenotype names (ClinVar):** Congenital stromal corneal dystrophy.

## Similar variants {#similar}

Related DCN variant pages (same residue, condition, or type): [DCN p.Leu265fs](/variant/dcn-p-leu265fs), [DCN p.Pro314Leu](/variant/dcn-p-pro314leu), [DCN p.Gly316fs](/variant/dcn-p-gly316fs), [DCN p.Lys321fs](/variant/dcn-p-lys321fs), [DCN p.Ser323fs](/variant/dcn-p-ser323fs), [DCN p.Lys187Arg](/variant/dcn-p-lys187arg), [DCN c.212-6T>C](/variant/dcn-c-212-minus-6t-c), [DCN c.*160C>T](/variant/dcn-c-star-160c-t).

### Data sources & attribution {#sources}

ClinVar (NCBI — public domain, built 2026-10-11); gnomAD v4.1 (Broad Institute, built 2026-10-06); AlphaMissense (Cheng et al. 2023, © Google DeepMind — CC BY 4.0, built 2026-01-27); REVEL (Ioannidis et al. 2016 — ODbL, built 2026-07-13); SaProt (Su et al. 2023 — MIT, built 2026-07-14); SpliceAI (Illumina — free for non-commercial use, built 2026-10-13); CADD (Rentzsch et al. 2019, University of Washington — free for non-commercial use, built 2026-10-10); Conservation (phyloP/phastCons/GERP) (UCSC hg38 470-way mammal (Hiller Lab) + Ensembl Compara, built 2026-07-12); gnomAD Non-coding Constraint (Gnocchi) (Chen et al. 2024, Broad Institute — CC0, built 2026-10-11); gnomAD Regional Missense Constraint (Broad Institute — CC0, built 2026-10-13); Pangolin (Zeng & Li 2022 — CC BY 4.0, built 2026-10-11); Repeat regions (UCSC — RepeatMasker, TRF, segmental duplications, built 2026-10-11); ClinGen (ClinGen, built 2026-09-22); UniProt (CC BY 4.0); Reactome / GO (CC BY 4.0, built 2026-09-23); MaveDB (per-record license, built 2026-10-11); CIViC (CC0, built 2026-09-22); Orphanet (Orphanet, built 2026-06-12)

*Primary record: NCBI ClinVar (variation 21302). Classifications reflect these databases as of the page's build date and may change. Free reference use — not medical advice; consult the primary submitters and a clinician.*