Is DOCK8 p.Ser1933= (c.5799C>T) pathogenic?

DOCK8 p.Ser1933= (c.5799C>T) is classified Conflicting classifications of pathogenicity in DOCK8 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-07-06). Very rare (popmax 0.00891%, eas); Associated with combined immunodeficiency due to DOCK8 deficiency.

What condition is associated with DOCK8 p.Ser1933= (c.5799C>T)?

DOCK8 p.Ser1933= (c.5799C>T) is associated with combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Ser1933= (c.5799C>T) in the general population?

DOCK8 p.Ser1933= (c.5799C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

DOCK8 p.Ser1933=

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.5799C>T · rs149602835 · VCV1337529

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

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 -9.5	GERP -5.3
Overall
CADD	4.179	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,886 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.00235% 38/1,614,048 alleles · very rare exomes 36/1,461,870 · genomes 2/152,178 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,222
Admixed American	0.00667%	15,000
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Finnishnot grpmax-eligible	0.00469%	21,343
European (non-Finnish)	0.00203%	49,168

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.Ser1933=
Coding: c.5799C>T
MANE Select: NM_203447
dbSNP: rs149602835
Type: single nucleotide variant
Location: chr9:446588 (GRCh38)
Gene constraint: LOEUF 0.622 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.17
Residue 1933: 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 p.Ser1933Arg 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-ser1933 (accessed [today's date]).

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