Is DOCK2 p.Gln30His (c.90G>C) pathogenic?

DOCK2 p.Gln30His (c.90G>C) is classified Conflicting classifications of pathogenicity in DOCK2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-04-01). AlphaMissense: likely benign (0.1664); Rare (popmax 0.776%, mid); Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Gln30His (c.90G>C)?

DOCK2 p.Gln30His (c.90G>C) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Gln30His (c.90G>C) in the general population?

DOCK2 p.Gln30His (c.90G>C) is rare (popmax 0.776%, mid) (gnomAD).

What do computational predictors say about DOCK2 p.Gln30His (c.90G>C)?

AlphaMissense predicts likely benign (score 0.1664) — an in-silico prediction, not a clinical call.

DOCK2 p.Gln30His

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.90G>C · rs141894939 · VCV542623

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1664 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.776%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DOCK2 deficiency

Computational evidence

Protein change
AlphaMissense	0.1664	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 63 kb · p 1.8e-09 · regional, not allelic
Overall
CADD	19.69	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.776% Middle Eastern · 47/6,058 alleles

Filtering AF 0.599% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.537%

Overall 0.111% 1,791/1,614,204 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.776%	129
African / African-American	0.489%	205
Admixed American	0.363%	275
Remaining individualsnot grpmax-eligible	0.189%	530
European (non-Finnish)	0.0873%	1,146
South Asian	0.00988%	10,120
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
Finnishnot grpmax-eligible	0.00156%	64,044

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.Gln30His
Coding: c.90G>C
MANE Select: NM_004946
dbSNP: rs141894939
Type: single nucleotide variant
Location: chr5:169654449 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 30: the sh3 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

INSYN2B p.Arg30His Uncertain significance ★ ⚠ 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
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

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-gln30his (accessed [today's date]).

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