Is DCDC2 p.Val184fs (c.549dup) pathogenic?

DCDC2 p.Val184fs (c.549dup) is classified Likely pathogenic in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-06-20). Absent from gnomAD; Associated with autosomal recessive nonsyndromic hearing loss 66.

What condition is associated with DCDC2 p.Val184fs (c.549dup)?

DCDC2 p.Val184fs (c.549dup) is associated with autosomal recessive nonsyndromic hearing loss 66, nephronophthisis 19, isolated neonatal sclerosing cholangitis (ClinVar).

How common is DCDC2 p.Val184fs (c.549dup) in the general population?

DCDC2 p.Val184fs (c.549dup) is absent from gnomAD (gnomAD).

DCDC2 p.Val184fs

c.549dup · rs1581640646 · VCV804454

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

autosomal recessive nonsyndromic hearing loss 66

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: DCDC2
Protein: p.Val184fs
Coding: c.549dup
MANE Select: NM_016356
dbSNP: rs1581640646
Type: Duplication
Location: chr6:24301722 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 184: the doublecortin 2 domain

Full DCDC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 66 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: nephronophthisis 19 isolated neonatal sclerosing cholangitis

Similar variants

DCDC2 p.Ala324fs Pathogenic/Likely pathogenic ★★ same condition
DCDC2 p.Ile177fs Pathogenic ★★ same condition
DCDC2 c.349-16dup Benign/Likely benign ★★ same condition
DCDC2 c.760-16dup Uncertain significance ★ same condition
DCDC2 c.294-2A>G Pathogenic ★★ same condition
DCDC2 c.349-2A>G Pathogenic ★★ same condition
DCDC2 c.705-2A>G Pathogenic ★★ same condition
DCDC2 p.Gly315fs Pathogenic/Likely pathogenic ★★ 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/dcdc2-p-val184fs (accessed [today's date]).

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