Is DOCK6 p.Leu1326fs (c.3975del) pathogenic?

DOCK6 p.Leu1326fs (c.3975del) is classified Pathogenic in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-16). Very rare (popmax 0.00223%, eas).

How common is DOCK6 p.Leu1326fs (c.3975del) in the general population?

DOCK6 p.Leu1326fs (c.3975del) is very rare (popmax 0.00223%, eas) (gnomAD).

DOCK6 p.Leu1326fs

c.3975del · rs1568227699 · VCV2001390

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 31 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.043	GERP -5.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,880 alleles

Overall 6.84e-05% 1/1,461,688 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.Leu1326fs
Coding: c.3975del
MANE Select: NM_020812
dbSNP: rs1568227699
Type: Deletion
Location: chr19:11215847 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB

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

Similar variants

DOCK6 p.Ala211fs Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Cys1061fs Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Leu1064fs Pathogenic ★★ same type
DOCK6 p.Ser1249fs Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Thr455fs Pathogenic/Likely pathogenic ★★ same type
DOCK6 p.Leu2037del Uncertain significance ★★ same type
DOCK6 c.5939+12del Benign/Likely benign ★★ same type
DOCK6 c.5235+1_5235+7del Likely pathogenic ★ 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/dock6-p-leu1326fs (accessed [today's date]).

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