Is DOCK2 p.Asn1384Ser (c.4151A>G) pathogenic?

DOCK2 p.Asn1384Ser (c.4151A>G) is classified Uncertain significance in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-20). AlphaMissense: likely benign (0.0544); Ultra-rare (popmax 0.0133%, afr); Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Asn1384Ser (c.4151A>G)?

DOCK2 p.Asn1384Ser (c.4151A>G) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Asn1384Ser (c.4151A>G) in the general population?

DOCK2 p.Asn1384Ser (c.4151A>G) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about DOCK2 p.Asn1384Ser (c.4151A>G)?

AlphaMissense predicts likely benign (score 0.0544) — an in-silico prediction, not a clinical call.

DOCK2 p.Asn1384Ser

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.4151A>G · rs375716929 · VCV567785

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0544 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DOCK2 deficiency

Computational evidence

Protein change
AlphaMissense	0.0544	likely benign
REVEL	0.111	moderately benign-leaning
SaProt	LLR -6.00	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 7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 33 kb · p 0.0025 · regional, not allelic
Overall
CADD	18.95	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0133% African / African-American · 10/74,932 alleles

Filtering AF 0.00826% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00774%

Overall 0.00805% 130/1,614,046 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,493
European (non-Finnish)	0.00975%	10,261
Remaining individualsnot grpmax-eligible	0.0064%	15,621
South Asian	0.0011%	91,082

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.Asn1384Ser
Coding: c.4151A>G
MANE Select: NM_004946
dbSNP: rs375716929
Type: single nucleotide variant
Location: chr5:170050335 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 1384: the docker domain; the 'interaction with crkl' region

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-asn1384ser (accessed [today's date]).

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