Is DOCK3 p.Arg1981fs (c.5941del) pathogenic?

DOCK3 p.Arg1981fs (c.5941del) is classified Uncertain significance in DOCK3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-06). Very rare (popmax 8.53e-05%, nfe); Associated with DOCK3-related disorder.

What condition is associated with DOCK3 p.Arg1981fs (c.5941del)?

DOCK3 p.Arg1981fs (c.5941del) is associated with DOCK3-related disorder (ClinVar).

How common is DOCK3 p.Arg1981fs (c.5941del) in the general population?

DOCK3 p.Arg1981fs (c.5941del) is very rare (popmax 8.53e-05%, nfe) (gnomAD).

DOCK3 p.Arg1981fs

c.5941del · rs1165491876 · VCV2634415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.53e-05%, nfe)

Conditions

DOCK3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	escapes	premature termination codon in the last exon (53 of 53) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.53e-05% European (non-Finnish) · 1/1,172,408 alleles

Overall 6.91e-05% 1/1,446,476 alleles · very rare

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: DOCK3
Protein: p.Arg1981fs
Coding: c.5941del
MANE Select: NM_004947
dbSNP: rs1165491876
Type: Deletion
Location: chr3:51381403 (GRCh38)
Gene constraint: LOEUF 0.298 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.52
Residue 1981: a UniProt-annotated variant site (in nedidha); the 'disordered' region

Full DOCK3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DOCK3-related disorder

Similar variants

DOCK3 p.Gly11_Val12insTer Uncertain significance ★ same condition
DOCK3 c.1037+1G>A Likely pathogenic ★ same condition
DOCK3 p.Arg362Ter Likely pathogenic ★ same condition
DOCK3 p.Ser847fs Likely pathogenic same condition
DOCK3 c.2548+6T>A Benign same condition
DOCK3 c.3915+10A>G Likely benign same condition
DOCK3 c.5412+10C>T Likely benign same condition
DOCK3 p.Asp1841= Likely benign 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/dock3-p-arg1981fs (accessed [today's date]).

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