Is DOK7 p.Trp100fs (c.298dup) pathogenic?

DOK7 p.Trp100fs (c.298dup) is classified Pathogenic in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-06). Absent from gnomAD; Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Trp100fs (c.298dup)?

DOK7 p.Trp100fs (c.298dup) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Trp100fs (c.298dup) in the general population?

DOK7 p.Trp100fs (c.298dup) is absent from gnomAD (gnomAD).

DOK7 p.Trp100fs

c.298dup · rs2474995471 · VCV2952641

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.053	GERP -1.9, phastCons 0.7

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DOK7
Protein: p.Trp100fs
Coding: c.298dup
MANE Select: NM_173660
dbSNP: rs2474995471
Type: Duplication
Location: chr4:3473602 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 100: the ph domain

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.Trp100Ter Pathogenic ★ same residue
DOK7 p.Ala378fs Pathogenic ★★ same condition
DOK7 p.Ala380fs Pathogenic ★★ same condition
DOK7 p.Gln460fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Glu382fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Gly496fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.His481fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Ser338fs 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-trp100fs (accessed [today's date]).

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