Is DCDC2 p.Asn469His (c.1405A>C) pathogenic?

DCDC2 p.Asn469His (c.1405A>C) is classified Uncertain significance in DCDC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0967); Very rare (popmax 0.000763%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DCDC2 p.Asn469His (c.1405A>C)?

DCDC2 p.Asn469His (c.1405A>C) is associated with Inborn genetic diseases (ClinVar).

How common is DCDC2 p.Asn469His (c.1405A>C) in the general population?

DCDC2 p.Asn469His (c.1405A>C) is very rare (popmax 0.000763%, nfe) (gnomAD).

What do computational predictors say about DCDC2 p.Asn469His (c.1405A>C)?

AlphaMissense predicts likely benign (score 0.0967) — an in-silico prediction, not a clinical call.

DCDC2 p.Asn469His

c.1405A>C · VCV4237982

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0967 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000763%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0967	likely benign
REVEL	0.078	moderately benign-leaning
SaProt	LLR -7.22	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 1.9	GERP 0.47, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	17.07	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 0.000763% European (non-Finnish) · 9/1,179,748 alleles

Filtering AF 0.000359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00026%

Overall 0.000616% 9/1,461,374 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.Asn469His
Coding: c.1405A>C
MANE Select: NM_016356
Type: single nucleotide variant
Location: chr6:24174756 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 469: 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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DCDC2 p.Asn469Thr Uncertain significance ★★ ⚠ same residue
DCDC2 p.Ala153Gly Uncertain significance ★★ ⚠ same condition
DCDC2 p.Ala356Pro Uncertain significance ★★ ⚠ same condition
DCDC2 p.Arg130His Uncertain significance ★★ ⚠ same condition
DCDC2 p.Arg379Lys Uncertain significance ★★ ⚠ same condition
DCDC2 p.Asn268Ser Uncertain significance ★★ ⚠ same condition
DCDC2 p.Glu326Asp Uncertain significance ★★ ⚠ same condition
DCDC2 p.Gly406Glu 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-asn469his (accessed [today's date]).

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