Is DOCK2 p.Lys286Ter (c.856A>T) pathogenic?

DOCK2 p.Lys286Ter (c.856A>T) is classified Likely pathogenic in DOCK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-12-19). Absent from gnomAD v4.1; Associated with DOCK2-related disorders.

What condition is associated with DOCK2 p.Lys286Ter (c.856A>T)?

DOCK2 p.Lys286Ter (c.856A>T) is associated with DOCK2-related disorders (ClinVar).

How common is DOCK2 p.Lys286Ter (c.856A>T) in the general population?

DOCK2 p.Lys286Ter (c.856A>T) is absent from gnomAD v4.1 (gnomAD).

DOCK2 p.Lys286Ter

c.856A>T · rs1581049599 · VCV636900

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DOCK2-related disorders

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 52
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.9, phastCons 1
Overall
CADD	39.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOCK2
Protein: p.Lys286Ter
Coding: c.856A>T
MANE Select: NM_004946
dbSNP: rs1581049599
Type: single nucleotide variant
Location: chr5:169695815 (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 disorders

Similar variants

DOCK2 p.Met120Ile Uncertain significance ★★ ⚠ same condition
DOCK2 p.Thr1809Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
DOCK2 p.Arg572= Likely benign same condition
DOCK2 c.169-11_169-7del Likely benign same condition
DOCK2 c.2267+3G>A Uncertain significance ★★ same type
DOCK2 c.2704-3C>T Uncertain significance ★★ same type
DOCK2 c.4467+4A>G Uncertain significance ★★ same type
DOCK2 p.Ala1393Val Uncertain significance ★★ ⚠ same type

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-lys286ter (accessed [today's date]).

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