Is DCN p.Ser325= (c.975G>A) pathogenic?

DCN p.Ser325= (c.975G>A) is classified Benign in DCN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-16). Low-frequency (popmax 1.42%, afr); Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Ser325= (c.975G>A)?

DCN p.Ser325= (c.975G>A) is associated with congenital stromal corneal dystrophy (ClinVar).

How common is DCN p.Ser325= (c.975G>A) in the general population?

DCN p.Ser325= (c.975G>A) is low-frequency (popmax 1.42%, 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.Ser325=

c.975G>A · rs80123678 · VCV310652

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.42%, afr)

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.101	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.29	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP -16	GERP -5
Overall
CADD	0.093	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.42% African / African-American · 1,061/74,944 alleles

Filtering AF 1.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.32%

Overall 0.0769% 1,241/1,613,424 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.42%	71
Remaining individualsnot grpmax-eligible	0.141%	710
Admixed American	0.107%	937
Middle Eastern	0.0825%	1,212
South Asian	0.00769%	13,006
European (non-Finnish)	0.00136%	73,724

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.Ser325=
Coding: c.975G>A
MANE Select: NM_001920
dbSNP: rs80123678
Type: single nucleotide variant
Location: chr12:91146163 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 88.60
Residue 325: 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.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-ser325 (accessed [today's date]).

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