Is DOCK2 p.His52fs (c.149dup) pathogenic?

DOCK2 p.His52fs (c.149dup) is classified Pathogenic in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-19). Absent from gnomAD; Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.His52fs (c.149dup)?

DOCK2 p.His52fs (c.149dup) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.His52fs (c.149dup) in the general population?

DOCK2 p.His52fs (c.149dup) is absent from gnomAD (gnomAD).

DOCK2 p.His52fs

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.149dup · rs2113279864 · VCV1454578

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 3 of 52
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.074	GERP -0.9, phastCons 0.001

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOCK2
Protein: p.His52fs
Coding: c.149dup
MANE Select: NM_004946
dbSNP: rs2113279864
Type: Duplication
Location: chr5:169669308 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 52: the sh3 domain; a β-strand

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.1483-17dup Benign ★★ same condition
DOCK2 p.Tyr106fs Pathogenic ★ same condition
INSYN2B p.Ala52Gly Uncertain significance ★ ⚠ same residue
DOCK2 c.1056-10dup Benign ★ same condition
DOCK2 c.1660-11dup Likely benign ★ same condition
DOCK2 c.2898+22_2898+23dup Likely benign ★ same condition
DOCK2 p.Leu1244fs Pathogenic same condition
DOCK2 c.2267+3G>A Uncertain significance ★★ 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-his52fs (accessed [today's date]).

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