Is DOCK8 p.Pro339= (c.1017G>A) pathogenic?

DOCK8 p.Pro339= (c.1017G>A) is classified Benign/Likely benign in DOCK8 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-28). Low-frequency (popmax 1.26%, afr); Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Pro339= (c.1017G>A)?

DOCK8 p.Pro339= (c.1017G>A) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Pro339= (c.1017G>A) in the general population?

DOCK8 p.Pro339= (c.1017G>A) is low-frequency (popmax 1.26%, afr) (gnomAD).

DOCK8 p.Pro339=

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.1017G>A · rs35746964 · VCV379115

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.26%, afr)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -5.4
Overall
CADD	3.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.26% African / African-American · 948/74,996 alleles

Filtering AF 1.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.17%

Overall 0.0679% 1,096/1,614,002 alleles · low-frequency exomes 553/1,461,766 · genomes 543/152,236 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.26%	79
Remaining individualsnot grpmax-eligible	0.0816%	1,225
Admixed American	0.0433%	2,308
Middle Eastern	0.0165%	6,060
South Asian	0.00878%	11,384
European (non-Finnish)	0.00517%	19,344
East Asian	0.00223%	44,866

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.Pro339=
Coding: c.1017G>A
MANE Select: NM_203447
dbSNP: rs35746964
Type: single nucleotide variant
Location: chr9:328144 (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.Pro339Leu Uncertain significance ★★ ⚠ 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
DOCK8 p.Arg1388Ter 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-pro339 (accessed [today's date]).

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