Is DOK7 p.Ser338fs (c.1001_1011dup) pathogenic?

DOK7 p.Ser338fs (c.10011011dup) is classified Pathogenic/Likely pathogenic in DOK7 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-03-13). Very rare (popmax 0.00135%, afr); Associated with fetal akinesia deformation sequence 3.

What condition is associated with DOK7 p.Ser338fs (c.1001_1011dup)?

DOK7 p.Ser338fs (c.1001_1011dup) is associated with fetal akinesia deformation sequence 3, congenital myasthenic syndrome 10, fetal akinesia deformation sequence 1 (ClinVar).

How common is DOK7 p.Ser338fs (c.1001_1011dup) in the general population?

DOK7 p.Ser338fs (c.1001_1011dup) is very rare (popmax 0.00135%, afr) (gnomAD).

DOK7 p.Ser338fs

c.1001_1011dup · rs1248986109 · VCV2203504

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00135%, afr)

Conditions

fetal akinesia deformation sequence 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (7 of 7) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP -0.2, phastCons 1
Overall
CADD	34.0	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 0.00135% African / African-American · 1/73,950 alleles

Filtering AF 0.000127% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000385% 6/1,556,810 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00135%	73,950
European (non-Finnish)	0.000433%	231,020

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.Ser338fs
Coding: c.1001_1011dup
MANE Select: NM_173660
dbSNP: rs1248986109
Type: Duplication
Location: chr4:3492986 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 338: the 'disordered' region

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

Disease context

fetal akinesia deformation sequence 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: congenital myasthenic syndrome 10 fetal akinesia deformation sequence 1

Similar variants

DOK7 p.Ser338= Likely benign ★ 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.Ser422fs 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-ser338fs (accessed [today's date]).

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