Is DOCK2 p.Tyr1315= (c.3945T>C) pathogenic?

DOCK2 p.Tyr1315= (c.3945T>C) is classified Benign in DOCK2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.38%, afr); Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Tyr1315= (c.3945T>C)?

DOCK2 p.Tyr1315= (c.3945T>C) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Tyr1315= (c.3945T>C) in the general population?

DOCK2 p.Tyr1315= (c.3945T>C) is low-frequency (popmax 3.38%, afr) (gnomAD).

DOCK2 p.Tyr1315=

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.3945T>C · rs34133853 · VCV476013

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.38%, afr)

Conditions

DOCK2 deficiency

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 -2.8	GERP -4.1
Overall
CADD	0.769	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.38% African / African-American · 2,538/75,034 alleles

Filtering AF 3.27% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.23%

Overall 0.174% 2,806/1,614,150 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.38%	30
Remaining individualsnot grpmax-eligible	0.211%	474
Admixed American	0.157%	639
Middle Eastern	0.132%	758
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
European (non-Finnish)	0.00254%	39,334
East Asian	0.00223%	44,872
South Asian	0.0022%	45,543

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.Tyr1315=
Coding: c.3945T>C
MANE Select: NM_004946
dbSNP: rs34133853
Type: single nucleotide variant
Location: chr5:170045884 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 1315: the docker domain; the 'interaction with crkl' region; an α-helix

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-tyr1315 (accessed [today's date]).

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