DOK7 p.Ser45=
c.135G>A · rs1336271146 · VCV2922524
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00668%, eas)
Conditions
2
fetal akinesia deformation sequence 1
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -15 | GERP -1.9 |
| Overall | ||
| CADD | 0.606 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00668%
East Asian · 3/44,878 alleles
Filtering AF
0.00177%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000891%
Overall
0.000372%
6/1,611,064 alleles · very rare
exomes 6/1,458,706 · genomes 0/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00668% | 14,959 |
| South Asian | 0.0022% | 45,490 |
| European (non-Finnish) | 8.48e-05% | 1,179,832 |
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.Ser45=
- Coding
- c.135G>A
- MANE Select
- NM_173660
- dbSNP
- rs1336271146
- Type
- single nucleotide variant
- Location
- chr4:3473440 (GRCh38)
- Gene constraint
- LOEUF 1.658 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 65.61
- Residue 45
- the ph domain; a UniProt-annotated variant site (does not affect achr clusters number or complexity)
Similar variants
- DOK7 p.Ser45Leu Benign/Likely benign ★★ 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-ser45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown