Is DOCK8 p.Arg1828Ter (c.5481dup) pathogenic?

DOCK8 p.Arg1828Ter (c.5481dup) is classified Pathogenic in DOCK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-12). Absent from gnomAD; Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Arg1828Ter (c.5481dup)?

DOCK8 p.Arg1828Ter (c.5481dup) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Arg1828Ter (c.5481dup) in the general population?

DOCK8 p.Arg1828Ter (c.5481dup) is absent from gnomAD (gnomAD).

DOCK8 p.Arg1828Ter

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.5481dup · rs2131814069 · VCV1071623

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 42 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1

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: DOCK8
Protein: p.Arg1828Ter
Coding: c.5481dup
MANE Select: NM_203447
dbSNP: rs2131814069
Type: Duplication
Location: chr9:441999 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 1828: 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.Asp1413fs Pathogenic ★★ same condition
DOCK8 p.Leu1059fs Pathogenic/Likely pathogenic ★★ same condition
DOCK8 p.Tyr2007fs Pathogenic ★★ same condition
DOCK8 c.3234+15dup Benign ★★ same condition
DOCK8 c.3234+21dup Benign/Likely benign ★★ same condition
DOCK8 p.Ala1170fs Pathogenic ★ same condition
DOCK8 p.Asn1395fs Likely pathogenic ★ same condition
DOCK8 p.Glu1680fs 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-arg1828ter (accessed [today's date]).

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