Is DCLK3 p.Asn657Asp (c.1969A>G) pathogenic?

DCLK3 p.Asn657Asp (c.1969A>G) is classified Uncertain significance in DCLK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: ambiguous (0.4001); Very rare (popmax 8.47e-05%, nfe).

How common is DCLK3 p.Asn657Asp (c.1969A>G) in the general population?

DCLK3 p.Asn657Asp (c.1969A>G) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about DCLK3 p.Asn657Asp (c.1969A>G)?

AlphaMissense predicts ambiguous (score 0.4001) — an in-silico prediction, not a clinical call.

DCLK3 p.Asn657Asp

c.1969A>G · VCV4009774

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4001 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4001	ambiguous
REVEL	0.106	moderately benign-leaning
SaProt	LLR -12.48	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.77	unconstrained · MANE · 22 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	23.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM N488D vs ClinVar N657D) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.84e-05% 1/1,461,842 alleles · very rare

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: DCLK3
Protein: p.Asn657Asp
Coding: c.1969A>G
MANE Select: NM_001394672
Type: single nucleotide variant
Location: chr3:36721650 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.27

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-asn657asp (accessed [today's date]).

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