Is DCN p.Pro220Ser (c.658C>T) pathogenic?

DCN p.Pro220Ser (c.658C>T) is classified Uncertain significance in DCN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely pathogenic (0.7191); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DCN p.Pro220Ser (c.658C>T)?

DCN p.Pro220Ser (c.658C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DCN p.Pro220Ser (c.658C>T) in the general population?

DCN p.Pro220Ser (c.658C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCN p.Pro220Ser (c.658C>T)?

AlphaMissense predicts likely pathogenic (score 0.7191) — an in-silico prediction, not a clinical call.

DCN p.Pro220Ser

c.658C>T · rs760152136 · VCV2616108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7191 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,569,634)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7191	likely pathogenic
REVEL	0.325	indeterminate
SaProt	LLR -9.50	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 1.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	29.1	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

No allele count reported in gnomAD v4.1 (AN 1,569,634). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DCN
Protein: p.Pro220Ser
Coding: c.658C>T
MANE Select: NM_001920
dbSNP: rs760152136
Type: single nucleotide variant
Location: chr12:91153184 (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.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.Arg57Cys 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-pro220ser (accessed [today's date]).

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