Is DOCK2 p.Arg444fs (c.1330_1331del) pathogenic?

DOCK2 p.Arg444fs (c.13301331del) is classified Pathogenic in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Arg444fs (c.1330_1331del)?

DOCK2 p.Arg444fs (c.1330_1331del) is associated with DOCK2 deficiency (ClinVar).

DOCK2 p.Arg444fs

Q: How is Combined immunodeficiency due to DOCK2 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1330_1331del · VCV3726565

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

DOCK2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 14 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.2, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: DOCK2
Protein: p.Arg444fs
Coding: c.1330_1331del
MANE Select: NM_004946
Type: Microsatellite
Location: chr5:169702372 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 444: the c2 dock-type domain

Full DOCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DOCK2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to DOCK2 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DOCK2 c.1482+6_1482+8del Uncertain significance ★ same condition
DOCK2 c.3233-9_3233-5del Uncertain significance ★ same condition
INSYN2B p.Arg444Gln Uncertain significance ★ ⚠ same residue
DOCK2 c.1056-18CT[2] Likely benign ★ same condition
DOCK2 c.1259-22TC[3] Likely benign ★ same condition
DOCK2 c.2031+4AG[3] Likely benign ★ same condition
DOCK2 c.2133-14_2133-12del Likely benign ★ same condition
DOCK2 c.2447+15_2447+17del Likely benign ★ same condition

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/dock2-p-arg444fs (accessed [today's date]).

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