Is DCDC2 p.Gln424Pro (c.1271A>C) pathogenic?

DCDC2 p.Gln424Pro (c.1271A>C) is classified Pathogenic in DCDC2 (ClinVar, No assertion criteria, 2 submitters; last evaluated 2015-01-18). AlphaMissense: likely benign (0.06); Very rare (popmax 8.47e-05%, nfe); Associated with Nonsyndromic Deafness.

What condition is associated with DCDC2 p.Gln424Pro (c.1271A>C)?

DCDC2 p.Gln424Pro (c.1271A>C) is associated with Nonsyndromic Deafness, autosomal recessive nonsyndromic hearing loss 66 (ClinVar).

How common is DCDC2 p.Gln424Pro (c.1271A>C) in the general population?

DCDC2 p.Gln424Pro (c.1271A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DCDC2 p.Gln424Pro (c.1271A>C)?

AlphaMissense predicts likely benign (score 0.06) — an in-silico prediction, not a clinical call.

DCDC2 p.Gln424Pro

c.1271A>C · rs794729665 · VCV161160

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.06 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Nonsyndromic Deafness

Computational evidence

Protein change
AlphaMissense	0.06	likely benign ⚠ discordant with ClinVar
REVEL	0.646	pathogenic-leaning
SaProt	LLR -5.41	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.9	GERP 0.59, phastCons 0.99
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	11.29	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,036 alleles

Overall 0.000137% 2/1,461,886 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	8.47e-05%	1,180,036

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Gln424Pro
Coding: c.1271A>C
MANE Select: NM_016356
dbSNP: rs794729665
Type: single nucleotide variant
Location: chr6:24178385 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 424: a UniProt-annotated variant site (in nsc); a UniProt-annotated variant site (in dfnb66; results in ciliary abnormalities including increased ciliary length); the 'disordered' region

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

Disease context

Nonsyndromic Deafness — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive nonsyndromic hearing loss 66

Similar variants

DCDC2 p.Gln424= Likely benign ★ 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-gln424pro (accessed [today's date]).

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