Is DOK7 p.Lys153Ter (c.457A>T) pathogenic?

DOK7 p.Lys153Ter (c.457A>T) is classified Pathogenic in DOK7 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-28). Absent from gnomAD v4.1; Associated with fetal akinesia deformation sequence 1.

What condition is associated with DOK7 p.Lys153Ter (c.457A>T)?

DOK7 p.Lys153Ter (c.457A>T) is associated with fetal akinesia deformation sequence 1, congenital myasthenic syndrome 10 (ClinVar).

How common is DOK7 p.Lys153Ter (c.457A>T) in the general population?

DOK7 p.Lys153Ter (c.457A>T) is absent from gnomAD v4.1 (gnomAD).

DOK7 p.Lys153Ter

c.457A>T · rs1727096342 · VCV853396

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

fetal akinesia deformation sequence 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 7
Splicing
SpliceAI	Δ0.25	acceptor loss, 31 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 7.3	GERP 1.3, phastCons 1
Overall
CADD	39.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DOK7
Protein: p.Lys153Ter
Coding: c.457A>T
MANE Select: NM_173660
dbSNP: rs1727096342
Type: single nucleotide variant
Location: chr4:3476467 (GRCh38)
Gene constraint: LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 65.61
Residue 153: the irs-type ptb 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.Lys153Thr Uncertain significance ★ ⚠ 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
DOK7 p.Arg201Ter Pathogenic ★★ same condition
DOK7 p.Cys412Ter 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-lys153ter (accessed [today's date]).

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