Is DOK7 p.Gln326fs (c.978_1018del) pathogenic?

DOK7 p.Gln326fs (c.9781018del) is classified Pathogenic in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). Very rare (popmax 8.68e-05%, nfe); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Gln326fs (c.978_1018del)?

DOK7 p.Gln326fs (c.978_1018del) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Gln326fs (c.978_1018del) in the general population?

DOK7 p.Gln326fs (c.978_1018del) is very rare (popmax 8.68e-05%, nfe) (gnomAD).

DOK7 p.Gln326fs

c.978_1018del · rs2109417797 · VCV1075034

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.68e-05%, nfe)

Conditions

congenital myasthenic syndrome 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.7	GERP 1.1, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.68e-05% European (non-Finnish) · 1/1,152,038 alleles

Overall 7.14e-05% 1/1,400,734 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: DOK7
Protein: p.Gln326fs
Coding: c.978_1018del
MANE Select: NM_173660
dbSNP: rs2109417797
Type: Deletion
Location: chr4:3492958 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 326: the 'disordered' region

Full DOK7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital myasthenic syndrome 10 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: fetal akinesia deformation sequence 1

Similar variants

DOK7 c.54+25_55-38del Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Asp433fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Cys442fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Ile199fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Leu454fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Leu466fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Lys320fs Pathogenic ★★ same condition
DOK7 p.Pro415fs Pathogenic/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/dok7-p-gln326fs (accessed [today's date]).

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