Is DOCK2 p.Ser585Ile (c.1754_1755delinsTT) pathogenic?

DOCK2 p.Ser585Ile (c.17541755delinsTT) is classified Uncertain significance in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-05). No gnomAD frequency available for this variant; Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Ser585Ile (c.1754_1755delinsTT)?

DOCK2 p.Ser585Ile (c.1754_1755delinsTT) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Ser585Ile (c.1754_1755delinsTT) in the general population?

DOCK2 p.Ser585Ile (c.1754_1755delinsTT) is no gnomAD frequency available for this variant (gnomAD).

DOCK2 p.Ser585Ile

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.1754_1755delinsTT · rs2532625136 · VCV3015772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

DOCK2 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 348 kb · p 3.1e-21 · regional, not allelic

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOCK2
Protein: p.Ser585Ile
Coding: c.1754_1755delinsTT
MANE Select: NM_004946
dbSNP: rs2532625136
Type: Indel
Location: chr5:169714122 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 585: 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 p.Ser585Arg Uncertain significance ★ ⚠ same residue
DOCK2 p.Ala312Lys Uncertain significance ★ same condition
DOCK2 p.Glu864Leu Uncertain significance ★ same condition
DOCK2 p.Met383_Lys384delinsIleGlu Uncertain significance ★ same condition
DOCK2 p.Ser585= Likely benign ★ same residue
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

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-ser585ile (accessed [today's date]).

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