DOCK4 p.Pro1742Ala
c.5224C>G · VCV3770456
Computational evidence
| Protein change | ||
| AlphaMissense | 0.0604 | likely benign |
|---|---|---|
| REVEL | 0.096 | moderately benign-leaning |
| SaProt | LLR -6.67 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 5.1 | GERP 0.78, phastCons 1 |
| Regional constraint | o/e 1.17 | unconstrained · MANE · 13 kb · p 0.00031 · regional, not allelic |
| Overall | ||
| CADD | 17.36 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P1733A vs ClinVar P1742A) — verify the residue.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Amishnot grpmax-eligible | 5.92% | 17 |
| Middle Easterngrpmax | 1.78% | 56 |
| Finnishnot grpmax-eligible | 1.56% | 64 |
| European (non-Finnish) | 1.18% | 85 |
| South Asian | 1.03% | 97 |
| Remaining individualsnot grpmax-eligible | 0.928% | 108 |
| Ashkenazi Jewishnot grpmax-eligible | 0.733% | 136 |
| Admixed American | 0.372% | 269 |
| African / African-American | 0.169% | 590 |
| East Asian | 0.00892% | 11,215 |
Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.
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
- DOCK4
- Protein
- p.Pro1742Ala
- Coding
- c.5224C>G
- MANE Select
- NM_001363540
- Type
- single nucleotide variant
- Location
- chr7:111739142 (GRCh38)
- Gene constraint
- LOEUF 0.445 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 76.47
- Residue 1742
- the 'disordered' region
Similar variants
- DOCK4 p.Arg490Trp Uncertain significance ★★ ⚠ same type
- DOCK4 p.Gln1223Arg Uncertain significance ★★ ⚠ same type
- DOCK4 p.His1716Tyr Uncertain significance ★★ ⚠ same type
- DOCK4 p.Pro1641Leu Uncertain significance ★★ ⚠ same type
- DOCK4 p.Ser750Arg Uncertain significance ★★ ⚠ same type
- DOCK4 c.550-8T>C Benign/Likely benign ★★ same type
- DOCK4 p.Arg106Cys Benign/Likely benign ★★ ⚠ same type
- DOCK4 p.Arg106His Benign/Likely benign ★★ 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/dock4-p-pro1742ala (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown