Is DCLK2 p.Arg762Cys (c.2284C>T) pathogenic?

DCLK2 p.Arg762Cys (c.2284C>T) is classified Uncertain significance in DCLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-22). AlphaMissense: likely benign (0.3059); Very rare (popmax 0.00587%, afr).

How common is DCLK2 p.Arg762Cys (c.2284C>T) in the general population?

DCLK2 p.Arg762Cys (c.2284C>T) is very rare (popmax 0.00587%, afr) (gnomAD).

What do computational predictors say about DCLK2 p.Arg762Cys (c.2284C>T)?

AlphaMissense predicts likely benign (score 0.3059) — an in-silico prediction, not a clinical call.

DCLK2 p.Arg762Cys

c.2284C>T · rs770526942 · VCV2533281

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3059 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00587%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3059	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -8.60	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 3.1	GERP 1.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 8,640 bp · p 0.47 · regional, not allelic
Overall
CADD	27.5	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

Grpmax group 0.00587% African / African-American · 4/68,104 alleles

Filtering AF 0.00197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00113%

Overall 0.00199% 30/1,507,860 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00587%	17,026
Admixed American	0.0043%	23,231
European (non-Finnish)	0.00204%	49,078
Finnishnot grpmax-eligible	0.00178%	56,116

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.Arg762Cys
Coding: c.2284C>T
MANE Select: NM_001040260
dbSNP: rs770526942
Type: single nucleotide variant
Location: chr4:150256230 (GRCh38)
Gene constraint: LOEUF 0.525 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 70.37
Residue 762: the 'disordered' region

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

Similar variants

DCLK2 p.Arg762His Uncertain significance ★ ⚠ same residue
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

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-arg762cys (accessed [today's date]).

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