Is DCN p.Lys142Glu (c.424A>G) pathogenic?

DCN p.Lys142Glu (c.424A>G) is classified Benign in DCN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.1715); Common (popmax 7.31%, amr) — too common for a highly-penetrant pathogenic allele; Associated with congenital stromal corneal dystrophy.

What condition is associated with DCN p.Lys142Glu (c.424A>G)?

DCN p.Lys142Glu (c.424A>G) is associated with congenital stromal corneal dystrophy (ClinVar).

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.Lys142Glu (c.424A>G)?

AlphaMissense predicts likely benign (score 0.1715) — an in-silico prediction, not a clinical call.

DCN p.Lys142Glu

Q: How common is DCN p.Lys142Glu (c.424A>G) in the general population?

DCN p.Lys142Glu (c.424A>G) is common (popmax 7.31%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.424A>G · rs142752401 · VCV310659

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1715 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 7.31%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital stromal corneal dystrophy

Computational evidence

Protein change
AlphaMissense	0.1715	likely benign
REVEL	0.196	benign-leaning
SaProt	LLR -11.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2.4, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	21.7	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 7.31% Admixed American · 4,386/60,016 alleles

Filtering AF 7.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.05%

Overall 0.292% 4,696/1,610,776 alleles · common

Ancestry group	Frequency	1 in
Admixed Americangrpmax	7.31%	14
Remaining individualsnot grpmax-eligible	0.191%	524
African / African-American	0.0547%	1,829
European (non-Finnish)	0.0126%	7,952
East Asian	0.00223%	44,856
South Asian	0.0011%	91,014

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.Lys142Glu
Coding: c.424A>G
MANE Select: NM_001920
dbSNP: rs142752401
Type: single nucleotide variant
Location: chr12:91158410 (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.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-lys142glu (accessed [today's date]).

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