Is DCN p.Pro48Thr (c.142C>A) pathogenic?

DCN p.Pro48Thr (c.142C>A) is classified Uncertain significance in DCN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-21). AlphaMissense: likely benign (0.0746); Ultra-rare (popmax 0.0112%, eas); Associated with Inborn genetic diseases.

What condition is associated with DCN p.Pro48Thr (c.142C>A)?

DCN p.Pro48Thr (c.142C>A) is associated with Inborn genetic diseases (ClinVar).

How common is DCN p.Pro48Thr (c.142C>A) in the general population?

DCN p.Pro48Thr (c.142C>A) is ultra-rare (popmax 0.0112%, eas) (gnomAD).

What do computational predictors say about DCN p.Pro48Thr (c.142C>A)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

DCN p.Pro48Thr

c.142C>A · rs1356510939 · VCV3080555

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.206	benign-leaning
SaProt	LLR -6.92	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 -3.2	GERP -4.5
Regional constraint	o/e 0.90	unconstrained · MANE · 32 kb · p 0.048 · regional, not allelic
Overall
CADD	6.64	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

Grpmax group 0.0112% East Asian · 5/44,842 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.000342% 5/1,461,850 alleles · ultra-rare

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.Pro48Thr
Coding: c.142C>A
MANE Select: NM_001920
dbSNP: rs1356510939
Type: single nucleotide variant
Location: chr12:91178411 (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-pro48thr (accessed [today's date]).

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