Is DOCK2 p.Ala1816Ser (c.5446G>T) pathogenic?

DOCK2 p.Ala1816Ser (c.5446G>T) is classified Benign/Likely benign in DOCK2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-23). AlphaMissense: likely benign (0.07); Rare (popmax 0.296%, nfe); Associated with DOCK2 deficiency.

What condition is associated with DOCK2 p.Ala1816Ser (c.5446G>T)?

DOCK2 p.Ala1816Ser (c.5446G>T) is associated with DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Ala1816Ser (c.5446G>T) in the general population?

DOCK2 p.Ala1816Ser (c.5446G>T) is rare (popmax 0.296%, nfe) (gnomAD).

What do computational predictors say about DOCK2 p.Ala1816Ser (c.5446G>T)?

AlphaMissense predicts likely benign (score 0.07) — an in-silico prediction, not a clinical call.

DOCK2 p.Ala1816Ser

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.5446G>T · rs144315682 · VCV542632

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.07 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.296%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DOCK2 deficiency

Computational evidence

Protein change
AlphaMissense	0.07	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.61	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 -0.65	GERP -2.5
Regional constraint	o/e 0.88	unconstrained · MANE · 33 kb · p 0.0025 · regional, not allelic
Overall
CADD	0.046	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 0.296% European (non-Finnish) · 3,496/1,180,022 alleles

Filtering AF 0.288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.285%

Overall 0.241% 3,890/1,614,154 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.296%	338
Remaining individualsnot grpmax-eligible	0.248%	403
Finnishnot grpmax-eligible	0.23%	435
Amishnot grpmax-eligible	0.11%	912
Admixed American	0.0666%	1,501
African / African-American	0.0653%	1,532
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
South Asian	0.0011%	91,076

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.Ala1816Ser
Coding: c.5446G>T
MANE Select: NM_004946
dbSNP: rs144315682
Type: single nucleotide variant
Location: chr5:170082811 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 80.40 · 6 PDB

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-ala1816ser (accessed [today's date]).

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