Is DCN p.Ile215Val (c.643A>G) pathogenic?

DCN p.Ile215Val (c.643A>G) is classified Uncertain significance in DCN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-25). AlphaMissense: likely benign (0.0834); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DCN p.Ile215Val (c.643A>G)?

DCN p.Ile215Val (c.643A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DCN p.Ile215Val (c.643A>G) in the general population?

DCN p.Ile215Val (c.643A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCN p.Ile215Val (c.643A>G)?

AlphaMissense predicts likely benign (score 0.0834) — an in-silico prediction, not a clinical call.

DCN p.Ile215Val

c.643A>G · VCV3838581

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0834 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,591,290)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0834	likely benign
REVEL	0.097	moderately benign-leaning
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 2.5, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	16.59	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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 1,591,290). 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.Ile215Val
Coding: c.643A>G
MANE Select: NM_001920
Type: single nucleotide variant
Location: chr12:91157084 (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-ile215val (accessed [today's date]).

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