Is DOK7 p.Pro426= (c.1278C>T) pathogenic?

DOK7 p.Pro426= (c.1278C>T) is classified Conflicting classifications of pathogenicity in DOK7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-04-01). Rare (popmax 0.31%, nfe); Associated with congenital myasthenic syndrome 10.

What condition is associated with DOK7 p.Pro426= (c.1278C>T)?

DOK7 p.Pro426= (c.1278C>T) is associated with congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Pro426= (c.1278C>T) in the general population?

DOK7 p.Pro426= (c.1278C>T) is rare (popmax 0.31%, nfe) (gnomAD).

DOK7 p.Pro426=

c.1278C>T · rs139468087 · VCV281424

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.31%, nfe)

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 -11	GERP -2
Overall
CADD	0.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.31% European (non-Finnish) · 3,658/1,179,480 alleles

Filtering AF 0.302% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.298%

Overall 0.251% 4,046/1,611,556 alleles · rare exomes 3,781/1,459,210 · genomes 265/152,346 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.31%	322
Finnishnot grpmax-eligible	0.261%	383
Remaining individualsnot grpmax-eligible	0.176%	567
Admixed American	0.0951%	1,052
African / African-American	0.056%	1,786
Middle Eastern	0.0495%	2,020
South Asian	0.011%	9,095
East Asian	0.00446%	22,422
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,548

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.Pro426=
Coding: c.1278C>T
MANE Select: NM_173660
dbSNP: rs139468087
Type: single nucleotide variant
Location: chr4:3493264 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 426: 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.Pro426Leu 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
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-pro426 (accessed [today's date]).

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