Is DOCK8 p.Val552= (c.1656A>G) pathogenic?

DOCK8 p.Val552= (c.1656A>G) is classified Conflicting classifications of pathogenicity in DOCK8 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-11-23). Ultra-rare (popmax 0.0164%, mid); Associated with DOCK8-related disorder.

What condition is associated with DOCK8 p.Val552= (c.1656A>G)?

DOCK8 p.Val552= (c.1656A>G) is associated with DOCK8-related disorder, combined immunodeficiency due to DOCK8 deficiency (ClinVar).

How common is DOCK8 p.Val552= (c.1656A>G) in the general population?

DOCK8 p.Val552= (c.1656A>G) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

DOCK8 p.Val552=

c.1656A>G · rs150595667 · VCV912463

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

DOCK8-related disorder

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 -8.5	GERP -3.7
Overall
CADD	0.044	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.00283% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00252%

Overall 0.00322% 52/1,614,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
African / African-American	0.00534%	18,734
European (non-Finnish)	0.00373%	26,818
East Asian	0.00223%	44,902
Remaining individualsnot grpmax-eligible	0.0016%	62,488
South Asian	0.0011%	91,084

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.Val552=
Coding: c.1656A>G
MANE Select: NM_203447
dbSNP: rs150595667
Type: single nucleotide variant
Location: chr9:340298 (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

DOCK8-related disorder

Also linked: combined immunodeficiency due to DOCK8 deficiency

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-val552 (accessed [today's date]).

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