Is DOCK8 p.Tyr982fs (c.2945_2958delinsTTTCTTG) pathogenic?

DOCK8 p.Tyr982fs (c.29452958delinsTTTCTTG) is classified Likely pathogenic in DOCK8 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-23). Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Tyr982fs (c.2945_2958delinsTTTCTTG)?

DOCK8 p.Tyr982fs (c.2945_2958delinsTTTCTTG) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

DOCK8 p.Tyr982fs

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.2945_2958delinsTTTCTTG · VCV4081348

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 24 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.4	GERP 2.8, phastCons 1

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

Variant & gene context

Gene: DOCK8
Protein: p.Tyr982fs
Coding: c.2945_2958delinsTTTCTTG
MANE Select: NM_203447
Type: Indel
Location: chr9:390541 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17

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.Tyr982= Conflicting classifications of pathogenicity ★ same residue
DOCK8 p.Tyr982Cys Uncertain significance ★ ⚠ same residue
DOCK8 c.3234+15_3234+16delinsAC Benign/Likely benign ★★ same condition
DOCK8 p.Asn413Gly Uncertain significance ★ same condition
DOCK8 p.Glu1811Gln Uncertain significance ★ same condition
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

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-tyr982fs (accessed [today's date]).

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