Is DOCK2 c.43+7G>C pathogenic?

DOCK2 c.43+7G>C is classified Likely benign in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-13). Absent from gnomAD v4.1; Associated with DOCK2 deficiency.

What condition is associated with DOCK2 c.43+7G>C?

DOCK2 c.43+7G>C is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 c.43+7G>C in the general population?

DOCK2 c.43+7G>C is absent from gnomAD v4.1 (gnomAD).

DOCK2 c.43+7G>C

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

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

VCV3659173

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DOCK2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
Splice region	donor +7	near-intronic (+7 nt from the splice site) · inside the BP7-excluded zone
SpliceAI	Δ0.31	donor loss, 3 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1	GERP -3.6, phastCons 0.44
Overall
CADD	9.426	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOCK2
Coding: c.43+7G>C
MANE Select: NM_004946
Type: single nucleotide variant
Location: chr5:169637376 (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.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
DOCK2 p.Ala454Val 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-43-plus-7g-c (accessed [today's date]).

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