Is DCLK2 p.Phe348Leu (c.1042T>C) pathogenic?

DCLK2 p.Phe348Leu (c.1042T>C) is classified Uncertain significance in DCLK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: ambiguous (0.4051); Very rare (popmax 0.00721%, nfe).

How common is DCLK2 p.Phe348Leu (c.1042T>C) in the general population?

DCLK2 p.Phe348Leu (c.1042T>C) is very rare (popmax 0.00721%, nfe) (gnomAD).

What do computational predictors say about DCLK2 p.Phe348Leu (c.1042T>C)?

AlphaMissense predicts ambiguous (score 0.4051) — an in-silico prediction, not a clinical call.

DCLK2 p.Phe348Leu

c.1042T>C · rs764965094 · VCV3080498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4051 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00721%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4051	ambiguous
REVEL	0.059	moderately benign-leaning
SaProt	LLR -4.75	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -2, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 153 kb · p 0.28 · regional, not allelic
Overall
CADD	17.68	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00721% European (non-Finnish) · 85/1,179,000 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00552% 89/1,612,834 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00721%	13,871
Remaining individualsnot grpmax-eligible	0.00641%	15,612

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.Phe348Leu
Coding: c.1042T>C
MANE Select: NM_001040260
dbSNP: rs764965094
Type: single nucleotide variant
Location: chr4:150203875 (GRCh38)
Gene constraint: LOEUF 0.525 · pLI 0.84 (gnomAD)
Structure: AlphaFold pLDDT 70.37
Residue 348: the 'disordered' region

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-phe348leu (accessed [today's date]).

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