Is DCDC2 p.Lys290Arg (c.869A>G) pathogenic?

DCDC2 p.Lys290Arg (c.869A>G) is classified Conflicting classifications of pathogenicity in DCDC2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-02-04). AlphaMissense: likely benign (0.0694); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with DCDC2 p.Lys290Arg (c.869A>G)?

DCDC2 p.Lys290Arg (c.869A>G) is associated with Inborn genetic diseases (ClinVar).

How common is DCDC2 p.Lys290Arg (c.869A>G) in the general population?

DCDC2 p.Lys290Arg (c.869A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about DCDC2 p.Lys290Arg (c.869A>G)?

AlphaMissense predicts likely benign (score 0.0694) — an in-silico prediction, not a clinical call.

DCDC2 p.Lys290Arg

c.869A>G · rs1561755265 · VCV598691

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0694	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.29	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 1.4	GERP -2.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	9.681	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 0.00223% East Asian · 1/44,858 alleles

Overall 6.84e-05% 1/1,461,506 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.Lys290Arg
Coding: c.869A>G
MANE Select: NM_016356
dbSNP: rs1561755265
Type: single nucleotide variant
Location: chr6:24278102 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 290: 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.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
DCDC2 p.Gly407Val 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-lys290arg (accessed [today's date]).

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