Is DCN p.Arg235= (c.703A>C) pathogenic?

DCN p.Arg235= (c.703A>C) is classified Benign in DCN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). Low-frequency (popmax 1.95%, afr); Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Arg235= (c.703A>C)?

DCN p.Arg235= (c.703A>C) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Arg235= (c.703A>C) in the general population?

DCN p.Arg235= (c.703A>C) is low-frequency (popmax 1.95%, afr) (gnomAD).

How is Congenital stromal corneal dystrophy inherited?

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

DCN p.Arg235=

c.703A>C · rs3138264 · VCV730961

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.95%, afr)

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.094	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2, phastCons 1
Overall
CADD	13.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.95% African / African-American · 1,462/74,962 alleles

Filtering AF 1.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.83%

Overall 0.0988% 1,592/1,611,190 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.95%	51
Remaining individualsnot grpmax-eligible	0.114%	879
Admixed American	0.0783%	1,277
Middle Eastern	0.033%	3,026
South Asian	0.0033%	30,345
European (non-Finnish)	0.000595%	168,203

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.Arg235=
Coding: c.703A>C
MANE Select: NM_001920
dbSNP: rs3138264
Type: single nucleotide variant
Location: chr12:91153139 (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.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-arg235 (accessed [today's date]).

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