Is DOCK6 p.Gln434fs (c.1300del) pathogenic?

DOCK6 p.Gln434fs (c.1300del) is classified Pathogenic in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-02). Very rare (popmax 0.00174%, amr); Associated with Adams-Oliver syndrome 2.

What condition is associated with DOCK6 p.Gln434fs (c.1300del)?

DOCK6 p.Gln434fs (c.1300del) is associated with Adams-Oliver syndrome 2 (ClinVar).

How common is DOCK6 p.Gln434fs (c.1300del) in the general population?

DOCK6 p.Gln434fs (c.1300del) is very rare (popmax 0.00174%, amr) (gnomAD).

DOCK6 p.Gln434fs

c.1300del · rs2147852182 · VCV1320060

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00174%, amr)

Conditions

Adams-Oliver syndrome 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 12 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -1.3, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% Admixed American · 1/57,516 alleles

Overall 6.91e-05% 1/1,447,498 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: DOCK6
Protein: p.Gln434fs
Coding: c.1300del
MANE Select: NM_020812
dbSNP: rs2147852182
Type: Deletion
Location: chr19:11243344 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 434: the 'disordered' region

Full DOCK6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Adams-Oliver syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DOCK6 p.Cys1061fs Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Leu1064fs Pathogenic ★★ same condition
DOCK6 p.Ser1249fs Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Thr455fs Pathogenic/Likely pathogenic ★★ same condition
DOCK6 p.Asp1316_Met1317insTer Pathogenic ★ same condition
DOCK6 p.Asp427fs Pathogenic ★ same condition
DOCK6 p.Glu1609fs Pathogenic ★ same condition
DOCK6 p.Glu1688fs Likely pathogenic ★ 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/dock6-p-gln434fs (accessed [today's date]).

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