Is DOCK6 p.His34fs (c.100dup) pathogenic?

DOCK6 p.His34fs (c.100dup) is classified Likely pathogenic in DOCK6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). Very rare (popmax 0.00027%, nfe).

How common is DOCK6 p.His34fs (c.100dup) in the general population?

DOCK6 p.His34fs (c.100dup) is very rare (popmax 0.00027%, nfe) (gnomAD).

DOCK6 p.His34fs

c.100dup · VCV4886518

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00027%, nfe)

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 2 of 48
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -0.49, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00027% European (non-Finnish) · 3/1,111,626 alleles

Filtering AF 7.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2e-05%

Overall 0.00023% 3/1,306,740 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.His34fs
Coding: c.100dup
MANE Select: NM_020812
Type: Duplication
Location: chr19:11253670 (GRCh38)
Gene constraint: LOEUF 0.87 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.78 · 7 PDB
Residue 34: the 'disordered' region

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

Similar variants

DOCK6 p.His34Asn Uncertain significance ★★ ⚠ same residue
DOCK6 p.His34Asp Conflicting classifications of pathogenicity ★ ⚠ same residue
DOCK6 c.2815-37_2815-17dup Benign/Likely benign ★★ same type
DOCK6 c.4022-2dup Benign ★★ same type
DOCK6 p.Arg429fs Pathogenic ★ same type
DOCK6 p.Cys1892fs Pathogenic ★ same type
DOCK6 p.Glu28fs Likely pathogenic ★ same type
DOCK6 p.Gly962fs 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-his34fs (accessed [today's date]).

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