Is DCDC2 p.Arg160= (c.478A>C) pathogenic?

DCDC2 p.Arg160= (c.478A>C) is classified Benign/Likely benign in DCDC2 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-03-01). Rare (popmax 0.189%, eas); Associated with autosomal recessive nonsyndromic hearing loss 66.

What condition is associated with DCDC2 p.Arg160= (c.478A>C)?

DCDC2 p.Arg160= (c.478A>C) is associated with autosomal recessive nonsyndromic hearing loss 66, nephronophthisis 19, isolated neonatal sclerosing cholangitis (ClinVar).

How common is DCDC2 p.Arg160= (c.478A>C) in the general population?

DCDC2 p.Arg160= (c.478A>C) is rare (popmax 0.189%, eas) (gnomAD).

DCDC2 p.Arg160=

c.478A>C · rs201204772 · VCV514414

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

rare (popmax 0.189%, eas)

Conditions

autosomal recessive nonsyndromic hearing loss 66

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	acceptor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 2.8	GERP 1.8, phastCons 1
Overall
CADD	10.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.189% East Asian · 85/44,880 alleles

Filtering AF 0.157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.145%

Overall 0.00979% 158/1,614,200 alleles · rare exomes 134/1,461,886 · genomes 24/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.189%	528
Remaining individualsnot grpmax-eligible	0.104%	962
Admixed American	0.00666%	15,006
European (non-Finnish)	0.000339%	295,009

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: DCDC2
Protein: p.Arg160=
Coding: c.478A>C
MANE Select: NM_016356
dbSNP: rs201204772
Type: single nucleotide variant
Location: chr6:24301794 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 160: the doublecortin 2 domain; an α-helix

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 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.Leu297Ter Pathogenic ★★ same condition
DCDC2 p.Met1Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
DCDC2 p.Ser128Ter Pathogenic/Likely pathogenic ★★ same condition
DCDC2 p.Ala384Gly Uncertain significance ★★ ⚠ same condition
DCDC2 p.Ala93Asp 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/dcdc2-p-arg160 (accessed [today's date]).

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