Is DCLK2 p.Arg130Gln (c.389G>A) pathogenic?

DCLK2 p.Arg130Gln (c.389G>A) is classified Uncertain significance in DCLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-01). AlphaMissense: likely benign (0.0814); Very rare (popmax 0.00684%, afr).

How common is DCLK2 p.Arg130Gln (c.389G>A) in the general population?

DCLK2 p.Arg130Gln (c.389G>A) is very rare (popmax 0.00684%, afr) (gnomAD).

What do computational predictors say about DCLK2 p.Arg130Gln (c.389G>A)?

AlphaMissense predicts likely benign (score 0.0814) — an in-silico prediction, not a clinical call.

DCLK2 p.Arg130Gln

c.389G>A · VCV4009762

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00684%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.312	indeterminate
SaProt	LLR -11.00	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP -1.4, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 153 kb · p 0.28 · regional, not allelic
Overall
CADD	24.3	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 0.00684% African / African-American · 5/73,142 alleles

Filtering AF 0.0026% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00165%

Overall 0.000579% 9/1,554,996 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00684%	14,628
Admixed American	0.00183%	54,504
European (non-Finnish)	0.000262%	381,876

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: DCLK2
Protein: p.Arg130Gln
Coding: c.389G>A
MANE Select: NM_001040260
Type: single nucleotide variant
Location: chr4:150079416 (GRCh38)
Gene constraint: LOEUF 0.525 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 70.37
Residue 130: the doublecortin 1 domain

Full DCLK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCLK2 c.961+930C>T Uncertain significance ★ same type
DCLK2 c.961+955A>G Uncertain significance ★ same type
DCLK2 c.961+963G>A Uncertain significance ★ same type
DCLK2 p.Ala176Val Uncertain significance ★ ⚠ same type
DCLK2 p.Ala178Val Uncertain significance ★ ⚠ same type
DCLK2 p.Ala27Gly Uncertain significance ★ ⚠ same type
DCLK2 p.Ala421Ser Uncertain significance ★ ⚠ same type
DCLK2 p.Ala49Glu 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/dclk2-p-arg130gln (accessed [today's date]).

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