Is DCDC2B p.Lys206Arg (c.617A>G) pathogenic?

DCDC2B p.Lys206Arg (c.617A>G) is classified Benign in DCDC2B (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-01). AlphaMissense: likely benign (0.0853); Rare (popmax 0.402%, nfe).

How common is DCDC2B p.Lys206Arg (c.617A>G) in the general population?

DCDC2B p.Lys206Arg (c.617A>G) is rare (popmax 0.402%, nfe) (gnomAD).

What do computational predictors say about DCDC2B p.Lys206Arg (c.617A>G)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

DCDC2B p.Lys206Arg

c.617A>G · rs200413736 · VCV2638607

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.402%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.483	indeterminate
SaProt	LLR -7.69	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 6.7	GERP 2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 6,800 bp · p 0.21 · regional, not allelic
Overall
CADD	24.4	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 0.402% European (non-Finnish) · 4,741/1,179,890 alleles

Filtering AF 0.392% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.388%

Overall 0.38% 6,135/1,614,026 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.52%	66
European (non-Finnish)grpmax	0.402%	249
Remaining individualsnot grpmax-eligible	0.358%	279
Admixed American	0.172%	583
Ashkenazi Jewishnot grpmax-eligible	0.0844%	1,184
South Asian	0.0494%	2,024
African / African-American	0.0333%	3,002
Middle Eastern	0.0165%	6,062

Finnish 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: DCDC2B
Protein: p.Lys206Arg
Coding: c.617A>G
MANE Select: NM_001099434
dbSNP: rs200413736
Type: single nucleotide variant
Location: chr1:32212579 (GRCh38)
Gene constraint: LOEUF 1.383 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.12
Residue 206: the doublecortin 2 domain

Full DCDC2B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCDC2B p.Ala125Pro Uncertain significance ★ ⚠ same type
DCDC2B p.Ala187Gly Uncertain significance ★ ⚠ same type
DCDC2B p.Ala239Ser Uncertain significance ★ ⚠ same type
DCDC2B p.Ala291Thr Uncertain significance ★ ⚠ same type
DCDC2B p.Ala346Val Uncertain significance ★ ⚠ same type
DCDC2B p.Ala55Ser Uncertain significance ★ ⚠ same type
DCDC2B p.Ala55Val Uncertain significance ★ ⚠ same type
DCDC2B p.Ala69Glu Uncertain significance ★ ⚠ same type

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/dcdc2b-p-lys206arg (accessed [today's date]).

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