Is DOK7 p.Arg452= (c.1356G>C) pathogenic?

DOK7 p.Arg452= (c.1356G>C) is classified Likely benign in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-10). Absent from gnomAD v4.1; Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Arg452= (c.1356G>C)?

DOK7 p.Arg452= (c.1356G>C) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Arg452= (c.1356G>C) in the general population?

DOK7 p.Arg452= (c.1356G>C) is absent from gnomAD v4.1 (gnomAD).

DOK7 p.Arg452=

c.1356G>C · rs1728663876 · VCV1138123

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

congenital myasthenic syndrome 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP -0.14, phastCons 1
Overall
CADD	4.443	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOK7
Protein: p.Arg452=
Coding: c.1356G>C
MANE Select: NM_173660
dbSNP: rs1728663876
Type: single nucleotide variant
Location: chr4:3493342 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 452: 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 p.Arg452Gln Uncertain significance ★★ ⚠ same residue
DOK7 p.Arg452Trp Uncertain significance ★★ ⚠ same residue
DOK7 c.331+1G>T Pathogenic ★★ same condition
DOK7 c.332-1G>A Likely pathogenic ★★ same condition
DOK7 c.332-1G>C Likely pathogenic ★★ same condition
DOK7 c.332-1G>T Likely pathogenic ★★ same condition
DOK7 p.Arg158Gln Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Arg201Ter 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-arg452 (accessed [today's date]).

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