Is DOCK2 p.Gln784= (c.2352A>G) pathogenic?

DOCK2 p.Gln784= (c.2352A>G) is classified Benign in DOCK2 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 7.52%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Gln784= (c.2352A>G)?

DOCK2 p.Gln784= (c.2352A>G) is associated with DOCK2 deficiency (ClinVar).

DOCK2 p.Gln784=

Q: How common is DOCK2 p.Gln784= (c.2352A>G) in the general population?

DOCK2 p.Gln784= (c.2352A>G) is common (popmax 7.52%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.2352A>G · rs13155521 · VCV476007

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 7.52%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

DOCK2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.66	donor gain · deltas
Pangolin	Δ0.41	gain · loss 0.05 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -0.29	GERP -2.2
Overall
CADD	15.99	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.52% European (non-Finnish) · 88,701/1,179,578 alleles

Filtering AF 7.48% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.46%

Overall 6.18% 99,643/1,613,356 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	7.52%	13
Remaining individualsnot grpmax-eligible	5.39%	19
Amishnot grpmax-eligible	4.93%	20
Finnishnot grpmax-eligible	4.47%	22
Ashkenazi Jewishnot grpmax-eligible	2.85%	35
Admixed American	2.27%	44
Middle Eastern	2.13%	47
South Asian	1.67%	60
African / African-American	1.08%	93
East Asian	0.0156%	6,405

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: DOCK2
Protein: p.Gln784=
Coding: c.2352A>G
MANE Select: NM_004946
dbSNP: rs13155521
Type: single nucleotide variant
Location: chr5:169747480 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB

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 p.Gln784Arg Uncertain significance ★ ⚠ same residue
DOCK2 c.2267+3G>A Uncertain significance ★★ same condition
DOCK2 c.2704-3C>T Uncertain significance ★★ same condition
DOCK2 c.4467+4A>G Uncertain significance ★★ same condition
DOCK2 p.Ala1393Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1710Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1765Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala24Pro 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-gln784 (accessed [today's date]).

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