DYNC2I2 p.Leu428=
c.1284G>A · VCV3699904
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Conditions
1
short-rib thoracic dysplasia 11 with or without polydactyly
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.24 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.1 | GERP 0.47, phastCons 0.24 |
| Overall | ||
| CADD | 4.488 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,052 alleles
Filtering AF
0.00583%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.000205%
3/1,461,100 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,026 |
| European (non-Finnish) | 8.48e-05% | 1,179,793 |
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
- DYNC2I2
- Protein
- p.Leu428=
- Coding
- c.1284G>A
- MANE Select
- NM_052844
- Type
- single nucleotide variant
- Location
- chr9:128634314 (GRCh38)
- Gene constraint
- LOEUF 1.036 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.66 · 4 PDB
Similar variants
- DYNC2I2 c.1372+1G>A Pathogenic/Likely pathogenic ★★ same condition
- DYNC2I2 p.Arg121Ter Pathogenic ★★ same condition
- DYNC2I2 p.Arg182Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
- DYNC2I2 p.Arg447Trp Pathogenic/Likely pathogenic ★★ same condition
- DYNC2I2 p.Ala131Val Uncertain significance ★★ ⚠ same condition
- DYNC2I2 p.Ala13Gly Uncertain significance ★★ ⚠ same condition
- DYNC2I2 p.Ala219Thr Uncertain significance ★★ ⚠ same condition
- DYNC2I2 p.Ala369Val Uncertain significance ★★ ⚠ 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/dync2i2-p-leu428 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown