DOK3 p.Ala321=
c.963G>A · VCV4244158
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00675%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -5.8 | GERP -2.2 |
| Overall | ||
| CADD | 0.72 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00675%
East Asian · 3/44,452 alleles
Filtering AF
0.00179%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0011%
Overall
0.00202%
32/1,583,492 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00675% | 14,817 |
| Remaining individualsnot grpmax-eligible | 0.00493% | 20,299 |
| South Asian | 0.00229% | 43,573 |
| European (non-Finnish) | 0.00198% | 50,520 |
| African / African-American | 0.00135% | 74,280 |
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
- DOK3
- Protein
- p.Ala321=
- Coding
- c.963G>A
- MANE Select
- NM_001308236
- Type
- single nucleotide variant
- Location
- chr5:177504343 (GRCh38)
- Gene constraint
- LOEUF 1.47 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 65.94
- Residue 321
- the 'disordered' region
Similar variants
- DOK3 p.Ala321Val Uncertain significance ★ ⚠ same residue
- DOK3 c.-102G>T Uncertain significance ★ ⚠ same type
- DOK3 c.-181C>T Uncertain significance ★ ⚠ same type
- DOK3 c.-182G>A Uncertain significance ★ ⚠ same type
- DOK3 c.-182G>C Uncertain significance ★ ⚠ same type
- DOK3 c.-23C>T Uncertain significance ★ ⚠ same type
- DOK3 c.-35G>A Uncertain significance ★ ⚠ same type
- DOK3 c.-62C>T Uncertain significance ★ ⚠ same type
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/dok3-p-ala321 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown