Is DCLK2 p.Tyr526Phe (c.1577A>T) pathogenic?

DCLK2 p.Tyr526Phe (c.1577A>T) is classified Uncertain significance in DCLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-19). AlphaMissense: likely benign (0.1622); Absent from gnomAD v4.1.

How common is DCLK2 p.Tyr526Phe (c.1577A>T) in the general population?

DCLK2 p.Tyr526Phe (c.1577A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DCLK2 p.Tyr526Phe (c.1577A>T)?

AlphaMissense predicts likely benign (score 0.1622) — an in-silico prediction, not a clinical call.

DCLK2 p.Tyr526Phe

c.1577A>T · rs2530974962 · VCV2619455

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1622 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1622	likely benign
REVEL	0.188	benign-leaning
SaProt	LLR -8.30	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 9.4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 15 kb · p 1.6e-07 · regional, not allelic
Overall
CADD	25.7	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.

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: DCLK2
Protein: p.Tyr526Phe
Coding: c.1577A>T
MANE Select: NM_001040260
dbSNP: rs2530974962
Type: single nucleotide variant
Location: chr4:150239752 (GRCh38)
Gene constraint: LOEUF 0.525 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 70.37
Residue 526: the protein kinase 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-tyr526phe (accessed [today's date]).

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