Is DOCK8 p.Arg2008Ter (c.6022C>T) pathogenic?

DOCK8 p.Arg2008Ter (c.6022C>T) is classified Pathogenic/Likely pathogenic in DOCK8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-19). Absent from gnomAD v4.1; Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Arg2008Ter (c.6022C>T)?

DOCK8 p.Arg2008Ter (c.6022C>T) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Arg2008Ter (c.6022C>T) in the general population?

DOCK8 p.Arg2008Ter (c.6022C>T) is absent from gnomAD v4.1 (gnomAD).

DOCK8 p.Arg2008Ter

Q: How is Combined immunodeficiency due to DOCK8 deficiency inherited?

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

c.6022C>T · rs1418593569 · VCV2868856

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

combined immunodeficiency due to DOCK8 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 46 of 48
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 2.2	GERP 1.6, phastCons 1
Overall
CADD	45.0	PHRED · no single calibrated threshold — expert panels disagree

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

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: DOCK8
Protein: p.Arg2008Ter
Coding: c.6022C>T
MANE Select: NM_203447
dbSNP: rs1418593569
Type: single nucleotide variant
Location: chr9:452071 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 2008: the docker domain

Full DOCK8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to DOCK8 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to DOCK8 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DOCK8 p.Arg2008Gln Uncertain significance ★ ⚠ same residue
DOCK8 c.1680-2A>G Likely pathogenic ★★ same condition
DOCK8 c.2779-2A>C Likely pathogenic ★★ same condition
DOCK8 c.2971-1G>A Pathogenic ★★ same condition
DOCK8 c.3530+1G>A Likely pathogenic ★★ same condition
DOCK8 c.528+1G>A Likely pathogenic ★★ same condition
DOCK8 c.529-2A>G Likely pathogenic ★★ same condition
DOCK8 p.Arg1388Ter Pathogenic ★★ 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/dock8-p-arg2008ter (accessed [today's date]).

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