Is DCN p.Lys187Arg (c.560A>G) pathogenic?

DCN p.Lys187Arg (c.560A>G) is classified Uncertain significance in DCN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-11). AlphaMissense: likely benign (0.0922); Very rare (popmax 0.00238%, nfe); Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Lys187Arg (c.560A>G)?

DCN p.Lys187Arg (c.560A>G) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Lys187Arg (c.560A>G) in the general population?

DCN p.Lys187Arg (c.560A>G) is very rare (popmax 0.00238%, nfe) (gnomAD).

How is Congenital stromal corneal dystrophy inherited?

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

What do computational predictors say about DCN p.Lys187Arg (c.560A>G)?

AlphaMissense predicts likely benign (score 0.0922) — an in-silico prediction, not a clinical call.

DCN p.Lys187Arg

c.560A>G · rs555705830 · VCV881299

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0922 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00238%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.0922	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 1.3, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	22.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00238% European (non-Finnish) · 28/1,177,528 alleles

Filtering AF 0.00165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00174% 28/1,611,274 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DCN
Protein: p.Lys187Arg
Coding: c.560A>G
MANE Select: NM_001920
dbSNP: rs555705830
Type: single nucleotide variant
Location: chr12:91157167 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 88.60

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 c.212-6T>C Benign ★★ same condition
DCN c.*160C>T Benign ★★ same condition
DCN c.*51A>G Benign ★★ same condition
DCN p.Ala11= Benign ★★ same condition
DCN p.Arg235= Benign ★★ same condition
DCN p.Ile177Phe Benign ★★ ⚠ same condition
DCN p.Lys142Glu Benign ★★ ⚠ same condition
DCN p.Pro18= Benign/Likely 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-lys187arg (accessed [today's date]).

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