Is DCN p.Arg57Cys (c.169C>T) pathogenic?

DCN p.Arg57Cys (c.169C>T) is classified Uncertain significance in DCN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely pathogenic (0.6827); Very rare (popmax 0.00401%, afr); Associated with Inborn genetic diseases.

What condition is associated with DCN p.Arg57Cys (c.169C>T)?

DCN p.Arg57Cys (c.169C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCN p.Arg57Cys (c.169C>T) in the general population?

DCN p.Arg57Cys (c.169C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DCN p.Arg57Cys (c.169C>T)?

AlphaMissense predicts likely pathogenic (score 0.6827) — an in-silico prediction, not a clinical call.

DCN p.Arg57Cys

c.169C>T · VCV4009811

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6827 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6827	likely pathogenic
REVEL	0.787	moderately pathogenic-leaning
SaProt	LLR -9.86	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	34.0	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 0.00401% African / African-American · 3/74,880 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00155% 25/1,613,844 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,960
Admixed American	0.00333%	29,988
East Asian	0.00223%	44,858
Remaining individualsnot grpmax-eligible	0.0016%	62,478
Finnishnot grpmax-eligible	0.00156%	64,008
European (non-Finnish)	0.00136%	73,749
South Asian	0.0011%	91,070

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.Arg57Cys
Coding: c.169C>T
MANE Select: NM_001920
Type: single nucleotide variant
Location: chr12:91178384 (GRCh38)
Gene constraint: LOEUF 0.789 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 88.60
Residue 57: a disulfide bond

Full DCN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCN p.Lys320Arg Uncertain significance ★★ ⚠ same condition
DCN p.Ala238Thr Uncertain significance ★ ⚠ same condition
DCN p.Ala289Thr Uncertain significance ★ ⚠ same condition
DCN p.Arg345Gly Uncertain significance ★ ⚠ same condition
DCN p.Arg350Cys Uncertain significance ★ ⚠ same condition
DCN p.Arg350His Uncertain significance ★ ⚠ same condition
DCN p.Arg44Gly Uncertain significance ★ ⚠ same condition
DCN p.Arg63Pro Uncertain significance ★ ⚠ 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-arg57cys (accessed [today's date]).

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