DOK7 p.Ala458fs
c.1372dup · rs2475116712 · VCV2943211
Pathogenic
Single submitter
Classification
Pathogenic
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
Consequence
frameshift
predicted LoF
gnomAD v4.1
Rare
ultra-rare (gnomAD MAF 2.165e-06)
Conditions
2
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 | 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 5.2 | GERP 1, phastCons 1 |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
dbSNP / gnomAD
Global frequency
0.000217%
via dbSNP · ultra-rare
No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.
Variant & gene context
- Gene
- DOK7
- Protein
- p.Ala458fs
- Coding
- c.1372dup
- MANE Select
- NM_173660
- dbSNP
- rs2475116712
- Type
- Duplication
- Location
- chr4:3493356 (GRCh38)
- Gene constraint
- LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 65.61
- Residue 458
- the 'disordered' region
Similar variants
- DOK7 p.Ala458Asp Uncertain significance ★★ ⚠ same residue
- DOK7 p.Ala458= 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
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-ala458fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown