Is DOCK2 p.Thr1779Ser (c.5335A>T) pathogenic?

DOCK2 p.Thr1779Ser (c.5335A>T) is classified Benign/Likely benign in DOCK2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-23). AlphaMissense: likely benign (0.0699); Low-frequency (popmax 1.12%, eas); Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Thr1779Ser (c.5335A>T)?

DOCK2 p.Thr1779Ser (c.5335A>T) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Thr1779Ser (c.5335A>T) in the general population?

DOCK2 p.Thr1779Ser (c.5335A>T) is low-frequency (popmax 1.12%, eas) (gnomAD).

What do computational predictors say about DOCK2 p.Thr1779Ser (c.5335A>T)?

AlphaMissense predicts likely benign (score 0.0699) — an in-silico prediction, not a clinical call.

DOCK2 p.Thr1779Ser

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.5335A>T · rs2270898 · VCV1167636

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0699 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.12%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DOCK2 deficiency

Computational evidence

Protein change
AlphaMissense	0.0699	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -5.69	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 0.44	GERP -3
Regional constraint	o/e 0.88	unconstrained · MANE · 33 kb · p 0.0025 · regional, not allelic
Overall
CADD	0.956	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 1.12% East Asian · 502/44,862 alleles

Filtering AF 1.04% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.01%

Overall 0.0319% 515/1,613,764 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.12%	89
Remaining individualsnot grpmax-eligible	0.016%	6,250
Admixed American	0.00167%	59,990
South Asian	0.0011%	91,060
European (non-Finnish)	8.47e-05%	1,179,954

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.Thr1779Ser
Coding: c.5335A>T
MANE Select: NM_004946
dbSNP: rs2270898
Type: single nucleotide variant
Location: chr5:170081889 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB
Residue 1779: a UniProt-annotated variant site (in)

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.Thr1779Ala 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-thr1779ser (accessed [today's date]).

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