Is DCDC2 p.Asn357Lys (c.1071C>A) pathogenic?

DCDC2 p.Asn357Lys (c.1071C>A) is classified Uncertain significance in DCDC2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-25). AlphaMissense: likely benign (0.0792); Very rare (popmax 0.00401%, afr); Associated with autosomal recessive nonsyndromic hearing loss 66.

What condition is associated with DCDC2 p.Asn357Lys (c.1071C>A)?

DCDC2 p.Asn357Lys (c.1071C>A) is associated with autosomal recessive nonsyndromic hearing loss 66, nephronophthisis 19, isolated neonatal sclerosing cholangitis (ClinVar).

How common is DCDC2 p.Asn357Lys (c.1071C>A) in the general population?

DCDC2 p.Asn357Lys (c.1071C>A) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about DCDC2 p.Asn357Lys (c.1071C>A)?

AlphaMissense predicts likely benign (score 0.0792) — an in-silico prediction, not a clinical call.

DCDC2 p.Asn357Lys

c.1071C>A · rs746347880 · VCV1416245

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 66

Computational evidence

Protein change
AlphaMissense	0.0792	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -5.72	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 0.66	GERP -2.8
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	0.282	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 0.00401% African / African-American · 3/74,886 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,738 alleles · very 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: DCDC2
Protein: p.Asn357Lys
Coding: c.1071C>A
MANE Select: NM_016356
dbSNP: rs746347880
Type: single nucleotide variant
Location: chr6:24178585 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 357: a UniProt-annotated variant site (in nsc); the 'disordered' region

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-asn357lys (accessed [today's date]).

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