Is DCN p.Lys321fs (c.962del) pathogenic?

DCN p.Lys321fs (c.962del) is classified Pathogenic in DCN (ClinVar, No assertion criteria, 2 submitters; last evaluated 2014-03-01). Absent from gnomAD v4.1; Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Lys321fs (c.962del)?

DCN p.Lys321fs (c.962del) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Lys321fs (c.962del) in the general population?

DCN p.Lys321fs (c.962del) is absent from gnomAD v4.1 (gnomAD).

How is Congenital stromal corneal dystrophy inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

DCN p.Lys321fs

c.962del · rs587777258 · VCV126374

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,576)

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (8 of 8) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.42	GERP 2.5, phastCons 0.99

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,613,576). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DCN
Protein: p.Lys321fs
Coding: c.962del
MANE Select: NM_001920
dbSNP: rs587777258
Type: Deletion
Location: chr12:91146176 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 88.60
Residue 321: a disulfide bond

Full DCN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital stromal corneal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital stromal corneal dystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Neonatal

Similar variants

DCN p.Leu265fs Likely pathogenic ★ same condition
DCN p.Gly316fs Pathogenic same condition
DCN p.Pro314fs Pathogenic same condition
DCN p.Ser323fs Pathogenic same condition
DCN p.Lys187Arg Uncertain significance ★★ ⚠ same condition
DCN c.212-6T>C Benign ★★ same condition
DCN c.*160C>T Benign ★★ same condition
DCN c.*51A>G Benign ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/dcn-p-lys321fs (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown