DOCK3 p.Ala1251=
c.3753C>T · VCV3353016
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0149%, sas)
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 -8 | GERP -5.4 |
| Overall | ||
| CADD | 2.025 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0149%
South Asian · 13/87,286 alleles
Filtering AF
0.00879%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00698%
Overall
0.00263%
42/1,597,646 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0149% | 6,714 |
| East Asian | 0.0067% | 14,926 |
| Remaining individualsnot grpmax-eligible | 0.00323% | 30,930 |
| European (non-Finnish) | 0.00205% | 48,844 |
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
- DOCK3
- Protein
- p.Ala1251=
- Coding
- c.3753C>T
- MANE Select
- NM_004947
- Type
- single nucleotide variant
- Location
- chr3:51339015 (GRCh38)
- Gene constraint
- LOEUF 0.298 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 75.52
- Residue 1251
- a UniProt-annotated variant site (in nedidha); the docker domain
Similar variants
- DOCK3 p.Arg1609Trp Uncertain significance ★★ ⚠ same type
- DOCK3 p.Arg1787Gln Uncertain significance ★★ ⚠ same type
- DOCK3 p.Arg2020Cys Uncertain significance ★★ ⚠ same type
- DOCK3 p.Arg392Gln Uncertain significance ★★ ⚠ same type
- DOCK3 p.Arg486His Uncertain significance ★★ ⚠ same type
- DOCK3 p.Gly1699Cys Uncertain significance ★★ ⚠ same type
- DOCK3 p.Leu1982Arg Uncertain significance ★★ ⚠ same type
- DOCK3 p.Lys1296Arg 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/dock3-p-ala1251 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown