DOCK6 p.Pro1448=
c.4344G>A · rs200307398 · VCV522330
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Rare
rare (popmax 0.548%, nfe)
Conditions
1
Adams-Oliver syndrome 2
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 -12 | GERP -5.2 |
| Overall | ||
| CADD | 8.098 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.548%
European (non-Finnish) · 6,467/1,179,362 alleles
Filtering AF
0.537%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.533%
Overall
0.439%
7,071/1,610,680 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.548% | 182 |
| Finnishnot grpmax-eligible | 0.385% | 259 |
| Remaining individualsnot grpmax-eligible | 0.286% | 350 |
| Middle Eastern | 0.158% | 635 |
| Amishnot grpmax-eligible | 0.11% | 912 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0947% | 1,056 |
| Admixed American | 0.0903% | 1,108 |
| African / African-American | 0.08% | 1,250 |
| South Asian | 0.033% | 3,026 |
| East Asian | 0.00446% | 22,411 |
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
- DOCK6
- Protein
- p.Pro1448=
- Coding
- c.4344G>A
- MANE Select
- NM_020812
- dbSNP
- rs200307398
- Type
- single nucleotide variant
- Location
- chr19:11213323 (GRCh38)
- Gene constraint
- LOEUF 0.87 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.78 · 7 PDB
Similar variants
- DOCK6 p.Pro1448Leu Uncertain significance ★★ ⚠ same residue
- DOCK6 p.Pro1448Thr Uncertain significance ★★ ⚠ same residue
- DOCK6 c.5939+2T>C Pathogenic ★★ same condition
- DOCK6 c.807-1G>A Likely pathogenic ★★ same condition
- DOCK6 p.Arg1526Ter Pathogenic/Likely pathogenic ★★ same condition
- DOCK6 p.Arg184Ter Pathogenic/Likely pathogenic ★★ same condition
- DOCK6 p.Arg488Ter Pathogenic/Likely pathogenic ★★ same condition
- DOCK6 p.Gln1188Ter 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/dock6-p-pro1448 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown