Is DOCK2 c.1843+9del pathogenic?

DOCK2 c.1843+9del is classified Likely benign in DOCK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-03). Rare (popmax 0.167%, afr); Associated with DOCK2 deficiency.

What condition is associated with DOCK2 c.1843+9del?

DOCK2 c.1843+9del is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 c.1843+9del in the general population?

DOCK2 c.1843+9del is rare (popmax 0.167%, afr) (gnomAD).

DOCK2 c.1843+9del

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

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

rs756542427 · VCV542620

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.167%, afr)

Conditions

DOCK2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -4.1, phastCons 0.002
Non-coding constraint	Z 2.83	1 kb window · o/e 0.81 · regional · uncalibrated
Overall
CADD	0.344	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.167% African / African-American · 125/74,750 alleles

Filtering AF 0.143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.134%

Overall 0.00842% 135/1,603,892 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.167%	598
Remaining individualsnot grpmax-eligible	0.00806%	12,405
Admixed American	0.00672%	14,892
European (non-Finnish)	8.52e-05%	1,173,210

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
Coding: c.1843+9del
MANE Select: NM_004946
dbSNP: rs756542427
Type: Deletion
Location: chr5:169714218 (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 c.1057del Likely pathogenic ★ same condition
DOCK2 p.Gly616fs Pathogenic ★ same condition
DOCK2 p.His907fs Pathogenic ★ same condition
DOCK2 p.Lys872fs Likely pathogenic ★ same condition
DOCK2 p.Met450fs Pathogenic ★ same condition
DOCK2 c.2031+3_2031+4del Uncertain significance ★ same condition
DOCK2 p.Asn920_Val923del Uncertain significance ★ same condition
DOCK2 p.Ile1741_Pro1742del 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-c-1843-plus-9del (accessed [today's date]).

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