Is DOK7 p.Arg201Ter (c.601C>T) pathogenic?

DOK7 p.Arg201Ter (c.601C>T) is classified Pathogenic in DOK7 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2024-09-28). Very rare (popmax 0.00111%, sas); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Arg201Ter (c.601C>T)?

DOK7 p.Arg201Ter (c.601C>T) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1, fetal akinesia deformation sequence 3 (ClinVar).

How common is DOK7 p.Arg201Ter (c.601C>T) in the general population?

DOK7 p.Arg201Ter (c.601C>T) is very rare (popmax 0.00111%, sas) (gnomAD).

DOK7 p.Arg201Ter

c.601C>T · rs118203995 · VCV1279

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00111%, sas)

Conditions

congenital myasthenic syndrome 10

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 7
REVEL	0.264	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -1.3, phastCons 0.69
Overall
CADD	43.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00111% South Asian · 1/90,210 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000344% 5/1,455,460 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00111%	90,210
European (non-Finnish)	0.00034%	294,241

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.Arg201Ter
Coding: c.601C>T
MANE Select: NM_173660
dbSNP: rs118203995
Type: single nucleotide variant
Location: chr4:3485607 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 201: the irs-type ptb domain

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 fetal akinesia deformation sequence 3

Similar variants

DOK7 p.Arg201Gln Uncertain significance ★ ⚠ same residue
DOK7 p.Arg201= Likely benign ★ 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.Cys412Ter 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-arg201ter (accessed [today's date]).

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