Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Common
common (popmax 32.5%, eas) — too common for a highly-penetrant pathogenic allele
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.067 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| Splice region | donor +240 | deep intronic (+240 nt into the intron) |
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -0.3 | GERP -3 |
| Overall | ||
| CADD | 0.185 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
32.5%
East Asian · 14,295/44,016 alleles
Filtering AF
32%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 31.8%
Overall
25.4%
408,000/1,603,846 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 32.5% | 3 |
| Finnishnot grpmax-eligible | 32% | 3 |
| European (non-Finnish) | 27.1% | 4 |
| Amishnot grpmax-eligible | 26.5% | 4 |
| Remaining individualsnot grpmax-eligible | 24.6% | 4 |
| Admixed American | 22.9% | 4 |
| Middle Eastern | 21.5% | 5 |
| South Asian | 19.3% | 5 |
| Ashkenazi Jewishnot grpmax-eligible | 15.1% | 7 |
| African / African-American | 4.53% | 22 |
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
- Coding
- c.53+240A>C
- MANE Select
- NM_203447
- dbSNP
- rs636922
- Type
- single nucleotide variant
- Location
- chr9:215269 (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 type
- DOCK8 c.2779-2A>C Likely pathogenic ★★ same type
- DOCK8 c.2971-1G>A Pathogenic ★★ same type
- DOCK8 c.3530+1G>A Likely pathogenic ★★ same type
- DOCK8 c.528+1G>A Likely pathogenic ★★ same type
- DOCK8 c.529-2A>G Likely pathogenic ★★ same type
- DOCK8 p.Arg1388Ter Pathogenic ★★ same type
- DOCK8 p.Arg1796Ter Pathogenic ★★ 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/dock8-c-53-plus-240a-c (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown