DOCK1 p.Ala495=
c.1485G>A · rs11595439 · VCV2640959
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.15%, mid)
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 -4.3 | GERP -5.2 |
| Overall | ||
| CADD | 4.718 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.15%
Middle Eastern · 70/6,062 alleles
Filtering AF
0.937%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.858%
Overall
0.319%
5,138/1,612,312 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.15% | 87 |
| European (non-Finnish) | 0.372% | 269 |
| Remaining individualsnot grpmax-eligible | 0.368% | 272 |
| Ashkenazi Jewishnot grpmax-eligible | 0.325% | 308 |
| South Asian | 0.194% | 516 |
| Admixed American | 0.137% | 730 |
| Finnishnot grpmax-eligible | 0.0907% | 1,103 |
| African / African-American | 0.056% | 1,785 |
| East Asian | 0.00223% | 44,864 |
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
- DOCK1
- Protein
- p.Ala495=
- Coding
- c.1485G>A
- MANE Select
- NM_001290223
- dbSNP
- rs11595439
- Type
- single nucleotide variant
- Location
- chr10:127024717 (GRCh38)
- Gene constraint
- LOEUF 0.637 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.63 · 1 PDB
- Residue 495
- the c2 dock-type domain; a β-strand
Similar variants
- DOCK1 p.Pro1783Ser Uncertain significance ★★ ⚠ same type
- DOCK1 p.Ala1185Thr Uncertain significance ★ ⚠ same type
- DOCK1 p.Ala151Thr Uncertain significance ★ ⚠ same type
- DOCK1 p.Ala1578Ser Uncertain significance ★ ⚠ same type
- DOCK1 p.Ala1590Gly Uncertain significance ★ ⚠ same type
- DOCK1 p.Ala1620Val Uncertain significance ★ ⚠ same type
- DOCK1 p.Ala1689Ser Uncertain significance ★ ⚠ same type
- DOCK1 p.Ala280Thr 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/dock1-p-ala495 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown