Is DCN p.Pro185Leu (c.554C>T) pathogenic?

DCN p.Pro185Leu (c.554C>T) is classified Uncertain significance in DCN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely pathogenic (0.707); Very rare (popmax 0.00246%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DCN p.Pro185Leu (c.554C>T)?

DCN p.Pro185Leu (c.554C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCN p.Pro185Leu (c.554C>T) in the general population?

DCN p.Pro185Leu (c.554C>T) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about DCN p.Pro185Leu (c.554C>T)?

AlphaMissense predicts likely pathogenic (score 0.707) — an in-silico prediction, not a clinical call.

DCN p.Pro185Leu

c.554C>T · rs139057073 · VCV2607693

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.707	likely pathogenic
REVEL	0.559	indeterminate
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	32.0	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 0.00246% European (non-Finnish) · 29/1,179,178 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00212% 31/1,460,914 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,661
East Asian	0.00223%	44,864
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Pro185Leu
Coding: c.554C>T
MANE Select: NM_001920
dbSNP: rs139057073
Type: single nucleotide variant
Location: chr12:91157173 (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

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

Similar variants

DCN p.Pro185= Likely benign ★ same residue
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

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-pro185leu (accessed [today's date]).

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