Is DCLK2 p.Ser484Leu (c.1451C>T) pathogenic?

DCLK2 p.Ser484Leu (c.1451C>T) is classified Uncertain significance in DCLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: ambiguous (0.3749); Ultra-rare (popmax 0.0491%, eas).

How common is DCLK2 p.Ser484Leu (c.1451C>T) in the general population?

DCLK2 p.Ser484Leu (c.1451C>T) is ultra-rare (popmax 0.0491%, eas) (gnomAD).

What do computational predictors say about DCLK2 p.Ser484Leu (c.1451C>T)?

AlphaMissense predicts ambiguous (score 0.3749) — an in-silico prediction, not a clinical call.

DCLK2 p.Ser484Leu

c.1451C>T · rs138420599 · VCV3080500

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3749 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0491%, eas)

Computational evidence

Protein change
AlphaMissense	0.3749	ambiguous
REVEL	0.363	indeterminate
SaProt	LLR -10.99	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 15 kb · p 1.6e-07 · regional, not allelic
Overall
CADD	27.8	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 0.0491% East Asian · 22/44,770 alleles

Filtering AF 0.0332% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.028%

Overall 0.00285% 46/1,612,608 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0491%	2,035
Remaining individualsnot grpmax-eligible	0.0144%	6,940
African / African-American	0.00806%	12,405
South Asian	0.0022%	45,492
European (non-Finnish)	0.000593%	168,503

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.Ser484Leu
Coding: c.1451C>T
MANE Select: NM_001040260
dbSNP: rs138420599
Type: single nucleotide variant
Location: chr4:150232713 (GRCh38)
Gene constraint: LOEUF 0.525 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 70.37
Residue 484: 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-ser484leu (accessed [today's date]).

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