Is DOCK2 p.Asp598Val (c.1793A>T) pathogenic?

DOCK2 p.Asp598Val (c.1793A>T) is classified Uncertain significance in DOCK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-27). AlphaMissense: likely pathogenic (0.9896); Very rare (popmax 0.00534%, nfe); Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Asp598Val (c.1793A>T)?

DOCK2 p.Asp598Val (c.1793A>T) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Asp598Val (c.1793A>T) in the general population?

DOCK2 p.Asp598Val (c.1793A>T) is very rare (popmax 0.00534%, nfe) (gnomAD).

What do computational predictors say about DOCK2 p.Asp598Val (c.1793A>T)?

AlphaMissense predicts likely pathogenic (score 0.9896) — an in-silico prediction, not a clinical call.

DOCK2 p.Asp598Val

Q: How is Combined immunodeficiency due to DOCK2 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1793A>T · VCV4243838

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9896 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00534%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DOCK2 deficiency

Computational evidence

Protein change
AlphaMissense	0.9896	likely pathogenic · top 8% in DOCK2
REVEL	0.714	pathogenic-leaning
SaProt	LLR -12.95	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.35 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 348 kb · p 3.1e-21 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00534% European (non-Finnish) · 63/1,179,626 alleles

Filtering AF 0.00427% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00388%

Overall 0.00397% 64/1,613,306 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00534%	18,724
Remaining individualsnot grpmax-eligible	0.0016%	62,464

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: DOCK2
Protein: p.Asp598Val
Coding: c.1793A>T
MANE Select: NM_004946
Type: single nucleotide variant
Location: chr5:169714161 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 598: the c2 dock-type domain

Full DOCK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DOCK2 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to DOCK2 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

DOCK2 c.2267+3G>A Uncertain significance ★★ same condition
DOCK2 c.2704-3C>T Uncertain significance ★★ same condition
DOCK2 c.4467+4A>G Uncertain significance ★★ same condition
DOCK2 p.Ala1393Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1710Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala1765Val Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala24Pro Uncertain significance ★★ ⚠ same condition
DOCK2 p.Ala454Val Uncertain significance ★★ ⚠ 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/dock2-p-asp598val (accessed [today's date]).

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