Is DCLK2 p.Ile511Val (c.1531A>G) pathogenic?

DCLK2 p.Ile511Val (c.1531A>G) is classified Uncertain significance in DCLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: likely benign (0.0924); Ultra-rare (popmax 0.0384%, nfe).

How common is DCLK2 p.Ile511Val (c.1531A>G) in the general population?

DCLK2 p.Ile511Val (c.1531A>G) is ultra-rare (popmax 0.0384%, nfe) (gnomAD).

What do computational predictors say about DCLK2 p.Ile511Val (c.1531A>G)?

AlphaMissense predicts likely benign (score 0.0924) — an in-silico prediction, not a clinical call.

DCLK2 p.Ile511Val

c.1531A>G · rs150687721 · VCV2212507

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0924 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0384%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0924	likely benign
REVEL	0.325	indeterminate
SaProt	LLR -9.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.57	unconstrained · MANE · 15 kb · p 1.6e-07 · regional, not allelic
Overall
CADD	23.6	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 0.0384% European (non-Finnish) · 453/1,179,988 alleles

Filtering AF 0.0354% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0343%

Overall 0.031% 500/1,614,126 alleles · ultra-rare exomes 466/1,461,820 · genomes 34/152,306 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0384%	2,605
Admixed American	0.035%	2,859
Remaining individualsnot grpmax-eligible	0.032%	3,125
African / African-American	0.00799%	12,508

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.Ile511Val
Coding: c.1531A>G
MANE Select: NM_001040260
dbSNP: rs150687721
Type: single nucleotide variant
Location: chr4:150232793 (GRCh38)
Gene constraint: LOEUF 0.525 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 70.37
Residue 511: 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-ile511val (accessed [today's date]).

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