Is DCDC2 p.His122= (c.366T>C) pathogenic?

DCDC2 p.His122= (c.366T>C) is classified Likely benign in DCDC2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-02). Rare (popmax 0.105%, eas); Associated with autosomal recessive nonsyndromic hearing loss 66.

What condition is associated with DCDC2 p.His122= (c.366T>C)?

DCDC2 p.His122= (c.366T>C) is associated with autosomal recessive nonsyndromic hearing loss 66, isolated neonatal sclerosing cholangitis (ClinVar).

How common is DCDC2 p.His122= (c.366T>C) in the general population?

DCDC2 p.His122= (c.366T>C) is rare (popmax 0.105%, eas) (gnomAD).

DCDC2 p.His122=

c.366T>C · rs200657247 · VCV2047908

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.105%, eas)

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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.1	GERP 0.1, phastCons 1
Overall
CADD	8.462	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% East Asian · 47/44,874 alleles

Filtering AF 0.0808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0725%

Overall 0.00316% 51/1,613,892 alleles · rare exomes 44/1,461,562 · genomes 7/152,330 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.105%	955
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00017%	589,953

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.His122=
Coding: c.366T>C
MANE Select: NM_016356
dbSNP: rs200657247
Type: single nucleotide variant
Location: chr6:24302027 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB

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 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-his122 (accessed [today's date]).

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