Is DOK7 p.Pro222fs (c.665del) pathogenic?

DOK7 p.Pro222fs (c.665del) is classified Likely pathogenic in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-03). Absent from gnomAD v4.1; Associated with fetal akinesia deformation sequence 3.

What condition is associated with DOK7 p.Pro222fs (c.665del)?

DOK7 p.Pro222fs (c.665del) is associated with fetal akinesia deformation sequence 3 (ClinVar).

How common is DOK7 p.Pro222fs (c.665del) in the general population?

DOK7 p.Pro222fs (c.665del) is absent from gnomAD v4.1 (gnomAD).

DOK7 p.Pro222fs

c.665del · rs1422350586 · VCV3241346

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,565,120)

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	predicted	premature termination codon in exon 6 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.3	GERP -2, phastCons 0.85

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,565,120). 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.Pro222fs
Coding: c.665del
MANE Select: NM_173660
dbSNP: rs1422350586
Type: Deletion
Location: chr4:3489685 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 222: 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

Similar variants

DOK7 c.54+25_55-38del Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Asp433fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Cys442fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Ile199fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 p.Pro415fs Pathogenic/Likely pathogenic ★★ same condition
DOK7 c.55-25_55-1del Likely pathogenic ★ same condition
DOK7 c.765_772+11del Likely pathogenic ★ same condition
DOK7 p.Ala302fs 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-pro222fs (accessed [today's date]).

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