Is DCN p.Pro18= (c.54G>A) pathogenic?

DCN p.Pro18= (c.54G>A) is classified Benign/Likely benign in DCN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-13). Rare (popmax 0.198%, mid); Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Pro18= (c.54G>A)?

DCN p.Pro18= (c.54G>A) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Pro18= (c.54G>A) in the general population?

DCN p.Pro18= (c.54G>A) is rare (popmax 0.198%, mid) (gnomAD).

How is Congenital stromal corneal dystrophy inherited?

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

DCN p.Pro18=

c.54G>A · rs145597441 · VCV310662

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.198%, mid)

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -14	GERP -5
Overall
CADD	1.428	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.198% Middle Eastern · 12/6,056 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0896%

Overall 0.0333% 537/1,613,706 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.198%	505
South Asian	0.103%	969
Remaining individualsnot grpmax-eligible	0.0544%	1,838
European (non-Finnish)	0.0312%	3,206
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,290
Admixed American	0.0217%	4,612
East Asian	0.0067%	14,933
African / African-American	0.00534%	18,725

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.Pro18=
Coding: c.54G>A
MANE Select: NM_001920
dbSNP: rs145597441
Type: single nucleotide variant
Location: chr12:91178499 (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
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

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-pro18 (accessed [today's date]).

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