Is DOCK8 p.Arg1008Trp (c.3022C>T) pathogenic?

DOCK8 p.Arg1008Trp (c.3022C>T) is classified Benign/Likely benign in DOCK8 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-01-29). AlphaMissense: likely pathogenic (0.581); Low-frequency (popmax 1.28%, afr); Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Arg1008Trp (c.3022C>T)?

DOCK8 p.Arg1008Trp (c.3022C>T) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Arg1008Trp (c.3022C>T) in the general population?

DOCK8 p.Arg1008Trp (c.3022C>T) is low-frequency (popmax 1.28%, afr) (gnomAD).

What do computational predictors say about DOCK8 p.Arg1008Trp (c.3022C>T)?

AlphaMissense predicts likely pathogenic (score 0.581) — an in-silico prediction, not a clinical call.

DOCK8 p.Arg1008Trp

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.3022C>T · rs16937932 · VCV178767

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely pathogenic

0.581 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

combined immunodeficiency due to DOCK8 deficiency

Computational evidence

Protein change
AlphaMissense	0.581	likely pathogenic
REVEL	0.28	benign-leaning
SaProt	LLR -11.49	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Regional constraint	o/e 1.15	unconstrained · MANE · 235 kb · p 6.4e-14 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.28% African / African-American · 958/75,000 alleles

Filtering AF 1.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.18%

Overall 0.0744% 1,201/1,614,060 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.28%	78
Remaining individualsnot grpmax-eligible	0.088%	1,136
Admixed American	0.0733%	1,364
Middle Eastern	0.033%	3,029
South Asian	0.0165%	6,071
European (non-Finnish)	0.0104%	9,594
East Asian	0.00891%	11,222

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.Arg1008Trp
Coding: c.3022C>T
MANE Select: NM_203447
dbSNP: rs16937932
Type: single nucleotide variant
Location: chr9:396836 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 1008: a UniProt-annotated variant site (in)

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.Arg1008Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
DOCK8 p.Arg1008= Likely benign ★ same residue
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
DOCK8 c.3530+1G>A Likely pathogenic ★★ same condition
DOCK8 c.528+1G>A Likely pathogenic ★★ same condition
DOCK8 c.529-2A>G Likely 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-arg1008trp (accessed [today's date]).

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