DOCK5 p.Ala1558=
c.4674C>T · VCV3777839
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0575%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -6.3 | GERP -4.5 |
| Overall | ||
| CADD | 3.419 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0575%
European (non-Finnish) · 678/1,179,834 alleles
Filtering AF
0.0538%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0524%
Overall
0.0487%
786/1,613,776 alleles · ultra-rare
exomes 716/1,461,656 · genomes 70/152,120 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0575% | 1,740 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0574% | 1,741 |
| Finnishnot grpmax-eligible | 0.0422% | 2,371 |
| Admixed American | 0.04% | 2,500 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,905 |
| African / African-American | 0.024% | 4,166 |
| East Asian | 0.00669% | 14,941 |
| South Asian | 0.00329% | 30,356 |
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
- DOCK5
- Protein
- p.Ala1558=
- Coding
- c.4674C>T
- MANE Select
- NM_024940
- Type
- single nucleotide variant
- Location
- chr8:25395689 (GRCh38)
- Gene constraint
- LOEUF 0.679 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 79.63 · 11 PDB
- Residue 1558
- the docker domain
Similar variants
- DOCK5 c.4788+9C>T Benign ★★ same type
- DOCK5 p.Leu986Phe Benign/Likely benign ★★ ⚠ same type
- DOCK5 p.Met987Leu Benign ★★ same type
- DOCK5 p.Pro1467= Benign ★★ same type
- DOCK5 p.Ser1306= Benign ★★ same type
- DOCK5 p.Thr469Met Benign/Likely benign ★★ ⚠ same type
- DOCK5 p.Ala1067Val Uncertain significance ★ ⚠ same type
- DOCK5 p.Ala1194Ser 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/dock5-p-ala1558 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown