Is DCN p.Gly356Arg (c.1066G>A) pathogenic?

DCN p.Gly356Arg (c.1066G>A) is classified Conflicting classifications of pathogenicity in DCN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-12). AlphaMissense: likely pathogenic (0.9705); Very rare (popmax 0.00446%, eas); Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Gly356Arg (c.1066G>A)?

DCN p.Gly356Arg (c.1066G>A) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Gly356Arg (c.1066G>A) in the general population?

DCN p.Gly356Arg (c.1066G>A) is very rare (popmax 0.00446%, eas) (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.Gly356Arg (c.1066G>A)?

AlphaMissense predicts likely pathogenic (score 0.9705) — an in-silico prediction, not a clinical call.

DCN p.Gly356Arg

c.1066G>A · rs775666283 · VCV883645

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9705 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9705	likely pathogenic
REVEL	0.619	indeterminate
SaProt	LLR -6.49	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,858 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000429%

Overall 0.00123% 18/1,461,382 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,429
South Asian	0.0022%	45,521
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,492
European (non-Finnish)	0.00102%	98,298

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.Gly356Arg
Coding: c.1066G>A
MANE Select: NM_001920
dbSNP: rs775666283
Type: single nucleotide variant
Location: chr12:91146072 (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 p.Lys187Arg Uncertain significance ★★ ⚠ same condition
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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

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-gly356arg (accessed [today's date]).

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