DOCK8 p.Lys276=
c.828G>A · rs1156965453 · VCV2144581
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0329%, mid)
Conditions
2
Inborn genetic diseases
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 1.6 | GERP -3.6, phastCons 1 |
| Overall | ||
| CADD | 10.06 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0329%
Middle Eastern · 2/6,084 alleles
Filtering AF
0.0058%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00241%
Overall
0.000868%
14/1,613,582 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0329% | 3,042 |
| South Asian | 0.00329% | 30,357 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,472 |
| European (non-Finnish) | 0.000678% | 147,464 |
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
- DOCK8
- Protein
- p.Lys276=
- Coding
- c.828G>A
- MANE Select
- NM_203447
- dbSNP
- rs1156965453
- Type
- single nucleotide variant
- Location
- chr9:325671 (GRCh38)
- Gene constraint
- LOEUF 0.622 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 75.17
Similar variants
- DOCK8 c.1680-2A>G Likely pathogenic ★★ same condition
- DOCK8 c.2779-2A>C Likely pathogenic ★★ same condition
- DOCK8 c.2971-1G>A Pathogenic ★★ same condition
- DOCK8 c.3530+1G>A Likely pathogenic ★★ same condition
- DOCK8 c.528+1G>A Likely pathogenic ★★ same condition
- DOCK8 c.529-2A>G Likely pathogenic ★★ same condition
- DOCK8 p.Arg1388Ter Pathogenic ★★ same condition
- DOCK8 p.Arg1796Ter 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/dock8-p-lys276 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown