Is DOK7 p.Pro390= (c.1170C>T) pathogenic?

DOK7 p.Pro390= (c.1170C>T) is classified Likely benign in DOK7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-22). Ultra-rare (popmax 0.0144%, sas); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Pro390= (c.1170C>T)?

DOK7 p.Pro390= (c.1170C>T) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Pro390= (c.1170C>T) in the general population?

DOK7 p.Pro390= (c.1170C>T) is ultra-rare (popmax 0.0144%, sas) (gnomAD).

DOK7 p.Pro390=

c.1170C>T · rs199525739 · VCV534134

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0144%, sas)

Conditions

fetal akinesia deformation sequence 1

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 -20	GERP -1.9
Overall
CADD	0.069	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0144% South Asian · 13/90,094 alleles

Filtering AF 0.00853% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00668%

Overall 0.00654% 105/1,605,378 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0144%	6,930
Admixed American	0.0118%	8,469
East Asian	0.00901%	11,103
European (non-Finnish)	0.00662%	15,094
Remaining individualsnot grpmax-eligible	0.00483%	20,711

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.Pro390=
Coding: c.1170C>T
MANE Select: NM_173660
dbSNP: rs199525739
Type: single nucleotide variant
Location: chr4:3493156 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61

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

Disease context

fetal akinesia deformation sequence 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 10

Similar variants

DOK7 p.Pro390Leu Uncertain significance ★★ ⚠ same residue
DOK7 p.Pro390Thr Uncertain significance ★★ ⚠ same residue
DOK7 p.Pro390Ser Conflicting classifications of pathogenicity ★ ⚠ 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

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-pro390 (accessed [today's date]).

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