Is DCDC2 p.Arg69Gln (c.206G>A) pathogenic?

DCDC2 p.Arg69Gln (c.206G>A) is classified Likely benign in DCDC2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-07). AlphaMissense: likely benign (0.1186); Rare (popmax 0.188%, sas); Associated with DCDC2-related disorder.

What condition is associated with DCDC2 p.Arg69Gln (c.206G>A)?

DCDC2 p.Arg69Gln (c.206G>A) is associated with DCDC2-related disorder (ClinVar).

How common is DCDC2 p.Arg69Gln (c.206G>A) in the general population?

DCDC2 p.Arg69Gln (c.206G>A) is rare (popmax 0.188%, sas) (gnomAD).

What do computational predictors say about DCDC2 p.Arg69Gln (c.206G>A)?

AlphaMissense predicts likely benign (score 0.1186) — an in-silico prediction, not a clinical call.

DCDC2 p.Arg69Gln

c.206G>A · rs568449358 · VCV3035838

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1186 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.188%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DCDC2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1186	likely benign
REVEL	0.542	indeterminate
SaProt	LLR -6.61	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.1, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 183 kb · p 0.62 · regional, not allelic
Overall
CADD	24.6	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 0.188% South Asian · 171/91,092 alleles

Filtering AF 0.165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.156%

Overall 0.0115% 186/1,613,542 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.188%	533
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0064%	15,626
European (non-Finnish)	0.000847%	118,003

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.Arg69Gln
Coding: c.206G>A
MANE Select: NM_016356
dbSNP: rs568449358
Type: single nucleotide variant
Location: chr6:24357545 (GRCh38)
Gene constraint: LOEUF 1.062 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.93 · 1 PDB
Residue 69: the doublecortin 1 domain

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

Disease context

DCDC2-related disorder

Similar variants

DCDC2 c.705-2A>G Pathogenic ★★ same condition
DCDC2 c.557+1G>T Pathogenic ★ same condition
DCDC2 p.Gln448Lys Uncertain significance ★ ⚠ same condition
DCDC2 p.Gln417Ter Likely pathogenic same condition
DCDC2 p.Gly368Glu Uncertain significance ⚠ same condition
DCDC2 p.Lys249Gln Uncertain significance ⚠ same condition
DCDC2 c.1326+6T>G Likely benign same condition
DCDC2 c.704+6T>C Likely benign 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-arg69gln (accessed [today's date]).

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