Is DOCK8 p.Asp187fs (c.560_561insAGCGA) pathogenic?

DOCK8 p.Asp187fs (c.560561insAGCGA) is classified Likely pathogenic in DOCK8 (ClinVar, Single submitter, 1 submitter). Absent from gnomAD; Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Asp187fs (c.560_561insAGCGA)?

DOCK8 p.Asp187fs (c.560_561insAGCGA) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Asp187fs (c.560_561insAGCGA) in the general population?

DOCK8 p.Asp187fs (c.560_561insAGCGA) is absent from gnomAD (gnomAD).

DOCK8 p.Asp187fs

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.560_561insAGCGA · rs2130697082 · VCV1339151

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

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	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 6 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	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.Asp187fs
Coding: c.560_561insAGCGA
MANE Select: NM_203447
dbSNP: rs2130697082
Type: Insertion
Location: chr9:311981 (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.Asp187Asn Uncertain significance ★★ ⚠ same residue
DOCK8 p.Asp187= Likely benign ★ same residue
DOCK8 c.3234+15_3234+16insCA Likely benign ★★ same condition
DOCK8 c.894+74_894+75insC Benign ★★ same condition
DOCK8 p.Asp1224fs Likely pathogenic ★ same condition
DOCK8 p.Ala951_Pro952insCys Uncertain significance ★ same condition
DOCK8 c.3234+10_3234+11insT Likely benign ★ same condition
DOCK8 c.3234+18_3234+19insT 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-asp187fs (accessed [today's date]).

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