Is DOCK8 p.Phe1113fs (c.3339del) pathogenic?

DOCK8 p.Phe1113fs (c.3339del) is classified Pathogenic/Likely pathogenic in DOCK8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-10-25). Very rare (popmax 0.00017%, nfe); Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Phe1113fs (c.3339del)?

DOCK8 p.Phe1113fs (c.3339del) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Phe1113fs (c.3339del) in the general population?

DOCK8 p.Phe1113fs (c.3339del) is very rare (popmax 0.00017%, nfe) (gnomAD).

DOCK8 p.Phe1113fs

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.3339del · rs748134881 · VCV872498

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

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 27 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP -0.003, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,548 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,254 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: DOCK8
Protein: p.Phe1113fs
Coding: c.3339del
MANE Select: NM_203447
dbSNP: rs748134881
Type: Deletion
Location: chr9:405015 (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.Phe1113Leu Uncertain significance ★★ ⚠ same residue
DOCK8 p.Leu1754fs 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
DOCK8 c.404+16del Benign/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-phe1113fs (accessed [today's date]).

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