Is DCLK3 p.Glu467Ala (c.1400A>C) pathogenic?

DCLK3 p.Glu467Ala (c.1400A>C) is classified Uncertain significance in DCLK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely benign (0.1012); Absent from gnomAD v4.1.

How common is DCLK3 p.Glu467Ala (c.1400A>C) in the general population?

DCLK3 p.Glu467Ala (c.1400A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCLK3 p.Glu467Ala (c.1400A>C)?

AlphaMissense predicts likely benign (score 0.1012) — an in-silico prediction, not a clinical call.

DCLK3 p.Glu467Ala

c.1400A>C · VCV4238088

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1012 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1012	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.95	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 2.2	GERP 0.26, phastCons 0.62
Regional constraint	o/e 1.02	unconstrained · MANE · 27 kb · p 0.67 · regional, not allelic
Overall
CADD	18.63	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM E298A vs ClinVar E467A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DCLK3
Protein: p.Glu467Ala
Coding: c.1400A>C
MANE Select: NM_001394672
Type: single nucleotide variant
Location: chr3:36737767 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.27
Residue 467: the protein kinase domain

Full DCLK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCLK3 p.Ala198Val Uncertain significance ★ ⚠ same type
DCLK3 p.Ala361Glu Uncertain significance ★ ⚠ same type
DCLK3 p.Ala405Thr Uncertain significance ★ ⚠ same type
DCLK3 p.Ala405Val Uncertain significance ★ ⚠ same type
DCLK3 p.Ala451Pro Uncertain significance ★ ⚠ same type
DCLK3 p.Ala755Thr Uncertain significance ★ ⚠ same type
DCLK3 p.Arg193Trp Uncertain significance ★ ⚠ same type
DCLK3 p.Arg323His 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/dclk3-p-glu467ala (accessed [today's date]).

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