Is DOCK2 p.Thr1809Ala (c.5425A>G) pathogenic?

DOCK2 p.Thr1809Ala (c.5425A>G) is classified Conflicting classifications of pathogenicity in DOCK2 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-02-06). AlphaMissense: likely benign (0.0784); Rare (popmax 0.345%, afr); Associated with DOCK2-related disorder.

What condition is associated with DOCK2 p.Thr1809Ala (c.5425A>G)?

DOCK2 p.Thr1809Ala (c.5425A>G) is associated with DOCK2-related disorder, DOCK2 deficiency (ClinVar).

How common is DOCK2 p.Thr1809Ala (c.5425A>G) in the general population?

DOCK2 p.Thr1809Ala (c.5425A>G) is rare (popmax 0.345%, afr) (gnomAD).

What do computational predictors say about DOCK2 p.Thr1809Ala (c.5425A>G)?

AlphaMissense predicts likely benign (score 0.0784) — an in-silico prediction, not a clinical call.

DOCK2 p.Thr1809Ala

c.5425A>G · rs146886839 · VCV542639

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.0784 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.345%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

DOCK2-related disorder

Computational evidence

Protein change
AlphaMissense	0.0784	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -6.57	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 0.42, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 33 kb · p 0.0025 · regional, not allelic
Overall
CADD	21.7	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 0.345% African / African-American · 259/75,032 alleles

Filtering AF 0.311% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.297%

Overall 0.0176% 284/1,613,900 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.345%	290
Remaining individualsnot grpmax-eligible	0.024%	4,167
Admixed American	0.015%	6,669
European (non-Finnish)	8.48e-05%	1,179,874

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.Thr1809Ala
Coding: c.5425A>G
MANE Select: NM_004946
dbSNP: rs146886839
Type: single nucleotide variant
Location: chr5:170081979 (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-related disorder

Also linked: DOCK2 deficiency

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-thr1809ala (accessed [today's date]).

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