Is DOCK8 p.Pro1944= (c.5832G>A) pathogenic?

DOCK8 p.Pro1944= (c.5832G>A) is classified Benign/Likely benign in DOCK8 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 15%, afr) — too common for a highly-penetrant pathogenic allele; Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Pro1944= (c.5832G>A)?

DOCK8 p.Pro1944= (c.5832G>A) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

DOCK8 p.Pro1944=

Q: How common is DOCK8 p.Pro1944= (c.5832G>A) in the general population?

DOCK8 p.Pro1944= (c.5832G>A) is common (popmax 15%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

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.5832G>A · rs10491684 · VCV137153

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 15%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

combined immunodeficiency due to DOCK8 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3	GERP -5.2
Overall
CADD	6.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 15% African / African-American · 11,205/74,906 alleles

Filtering AF 14.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 14.6%

Overall 7.18% 115,751/1,612,724 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	15%	7
Ashkenazi Jewishnot grpmax-eligible	9.32%	11
Middle Eastern	8.66%	12
Finnishnot grpmax-eligible	8.52%	12
Remaining individualsnot grpmax-eligible	7.19%	14
European (non-Finnish)	7.17%	14
Admixed American	5.01%	20
South Asian	4.15%	24
Amishnot grpmax-eligible	2.53%	40
East Asian	0.0267%	3,739

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.Pro1944=
Coding: c.5832G>A
MANE Select: NM_203447
dbSNP: rs10491684
Type: single nucleotide variant
Location: chr9:449798 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 1944: 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 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
DOCK8 p.Arg1388Ter Pathogenic ★★ same condition
DOCK8 p.Arg1796Ter 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-pro1944 (accessed [today's date]).

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