Is DCDC2 p.Ser239= (c.717T>G) pathogenic?

DCDC2 p.Ser239= (c.717T>G) is classified Likely benign in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-13). Very rare (popmax 0.00255%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 66.

What condition is associated with DCDC2 p.Ser239= (c.717T>G)?

DCDC2 p.Ser239= (c.717T>G) is associated with autosomal recessive nonsyndromic hearing loss 66, isolated neonatal sclerosing cholangitis (ClinVar).

How common is DCDC2 p.Ser239= (c.717T>G) in the general population?

DCDC2 p.Ser239= (c.717T>G) is very rare (popmax 0.00255%, nfe) (gnomAD).

DCDC2 p.Ser239=

c.717T>G · VCV4790073

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00255%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 66

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.59, phastCons 1
Overall
CADD	9.829	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00255% European (non-Finnish) · 30/1,176,712 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00194% 31/1,601,886 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00255%	39,224
Remaining individualsnot grpmax-eligible	0.00161%	62,012

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.Ser239=
Coding: c.717T>G
MANE Select: NM_016356
Type: single nucleotide variant
Location: chr6:24288894 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 239: 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: isolated neonatal sclerosing cholangitis

Similar variants

DCDC2 p.Ser239Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
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

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-ser239 (accessed [today's date]).

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