Is DCLK3 p.Met628Val (c.1882A>G) pathogenic?

DCLK3 p.Met628Val (c.1882A>G) is classified Uncertain significance in DCLK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely benign (0.0872); Ultra-rare (popmax 0.0165%, mid).

How common is DCLK3 p.Met628Val (c.1882A>G) in the general population?

DCLK3 p.Met628Val (c.1882A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about DCLK3 p.Met628Val (c.1882A>G)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

DCLK3 p.Met628Val

c.1882A>G · rs775498135 · VCV2518321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.066	moderately benign-leaning
SaProt	LLR -7.43	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 0.85	GERP -2.5, phastCons 0.72
Regional constraint	o/e 0.77	unconstrained · MANE · 22 kb · p 2.4e-05 · regional, not allelic
Overall
CADD	17.04	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM M459V vs ClinVar M628V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.0013% 21/1,614,220 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00878%	11,386
Admixed American	0.00167%	60,030
European (non-Finnish)	0.000932%	107,276

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.Met628Val
Coding: c.1882A>G
MANE Select: NM_001394672
dbSNP: rs775498135
Type: single nucleotide variant
Location: chr3:36737285 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.27
Residue 628: the 'disordered' region

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-met628val (accessed [today's date]).

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