Is DOCK8 p.Lys1855fs (c.5564del) pathogenic?

DOCK8 p.Lys1855fs (c.5564del) is classified Likely pathogenic in DOCK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Lys1855fs (c.5564del)?

DOCK8 p.Lys1855fs (c.5564del) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

DOCK8 p.Lys1855fs

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.5564del · VCV3597472

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 43 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -0.27, phastCons 1

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

Variant & gene context

Gene: DOCK8
Protein: p.Lys1855fs
Coding: c.5564del
MANE Select: NM_203447
Type: Deletion
Location: chr9:443499 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 1855: 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.Lys1855Asn Uncertain significance ★ ⚠ same residue
DOCK8 p.Leu1754fs Pathogenic ★★ same condition
DOCK8 p.Phe1113fs Pathogenic/Likely pathogenic ★★ same condition
DOCK8 p.Tyr491fs Pathogenic ★★ same condition
DOCK8 c.2109+11del Benign/Likely benign ★★ same condition
DOCK8 c.3234+15del Benign/Likely benign ★★ same condition
DOCK8 c.3234+8del Benign ★★ same condition
DOCK8 c.333-8del Likely benign ★★ 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-lys1855fs (accessed [today's date]).

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