Is DOK7 c.331+9C>T pathogenic?

DOK7 c.331+9C>T is classified Conflicting classifications of pathogenicity in DOK7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-20). Rare (popmax 0.185%, nfe); Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 c.331+9C>T?

DOK7 c.331+9C>T is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 c.331+9C>T in the general population?

DOK7 c.331+9C>T is rare (popmax 0.185%, nfe) (gnomAD).

DOK7 c.331+9C>T

rs370879328 · VCV196595

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.185%, nfe)

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +9	near-intronic (+9 nt from the splice site)
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.4	GERP -1.3
Overall
CADD	9.751	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.185% European (non-Finnish) · 2,105/1,138,112 alleles

Filtering AF 0.178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.176%

Overall 0.144% 2,213/1,541,634 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.185%	541
Remaining individualsnot grpmax-eligible	0.0808%	1,238
Admixed American	0.0579%	1,729
African / African-American	0.0355%	2,818
Ashkenazi Jewishnot grpmax-eligible	0.00354%	28,258
East Asian	0.00243%	41,204
Finnishnot grpmax-eligible	0.00168%	59,408
South Asian	0.00118%	84,874

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
Coding: c.331+9C>T
MANE Select: NM_173660
dbSNP: rs370879328
Type: single nucleotide variant
Location: chr4:3473645 (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 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
DOK7 p.Gln151Ter 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-c-331-plus-9c-t (accessed [today's date]).

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