DYNC2I2 p.Val450=
c.1350T>A · rs200052239 · VCV707471
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
rare (popmax 0.869%, eas)
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 | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2 | GERP -0.69, phastCons 1 |
| Overall | ||
| CADD | 7.541 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.869%
East Asian · 390/44,876 alleles
Filtering AF
0.798%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.77%
Overall
0.0291%
469/1,613,812 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.869% | 115 |
| Remaining individualsnot grpmax-eligible | 0.0336% | 2,977 |
| Middle Eastern | 0.0165% | 6,060 |
| South Asian | 0.0154% | 6,506 |
| European (non-Finnish) | 0.00356% | 28,095 |
| African / African-American | 0.00133% | 75,046 |
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.Val450=
- Coding
- c.1350T>A
- MANE Select
- NM_052844
- dbSNP
- rs200052239
- Type
- single nucleotide variant
- Location
- chr9:128634248 (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-val450 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown