Is DCLK3 p.Pro398Ser (c.1192C>T) pathogenic?

DCLK3 p.Pro398Ser (c.1192C>T) is classified Uncertain significance in DCLK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.0742); Very rare (popmax 0.0011%, sas).

How common is DCLK3 p.Pro398Ser (c.1192C>T) in the general population?

DCLK3 p.Pro398Ser (c.1192C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about DCLK3 p.Pro398Ser (c.1192C>T)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

DCLK3 p.Pro398Ser

c.1192C>T · VCV4658743

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -5.73	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 1.3	GERP -0.45, phastCons 0.019
Regional constraint	o/e 1.02	unconstrained · MANE · 27 kb · p 0.67 · regional, not allelic
Overall
CADD	2.503	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 P229S vs ClinVar P398S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,076 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000342% 5/1,461,884 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,076
European (non-Finnish)	0.000339%	295,002

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.Pro398Ser
Coding: c.1192C>T
MANE Select: NM_001394672
Type: single nucleotide variant
Location: chr3:36737975 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.27
Residue 398: the protein kinase domain

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-pro398ser (accessed [today's date]).

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