DOK7 p.Pro504fs
c.1508dup · rs773220689 · VCV1138003
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 4.8 | GERP -0.083, phastCons 1 |
| Overall | ||
| CADD | 32.0 | PHRED · no single calibrated threshold — expert panels disagree |
Predicted loss-of-function is descriptive, not an applied PVS1 code.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Finnishnot grpmax-eligible | 0.318% | 315 |
| Remaining individualsnot grpmax-eligible | 0.0112% | 8,902 |
| East Asiangrpmax | 0.00446% | 22,403 |
| European (non-Finnish) | 0.00161% | 62,060 |
| South Asian | 0.0011% | 90,778 |
Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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.Pro504fs
- Coding
- c.1508dup
- MANE Select
- NM_173660
- dbSNP
- rs773220689
- Type
- Duplication
- Location
- chr4:3493488 (GRCh38)
- Gene constraint
- LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 65.61
Disease context
Also linked: congenital myasthenic syndrome 10fetal akinesia deformation sequence 1
Similar variants
- DOK7 p.Pro504_Ter505delinsArg Pathogenic/Likely pathogenic ★★ same residue
- DOK7 p.Pro504Thr Uncertain significance ★ ⚠ 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-pro504fs (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown