DYNC2I2 p.Ala219=
c.657T>C · rs761447438 · VCV2792081
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000597%, nfe)
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 -9.1 | GERP -3.7 |
| Overall | ||
| CADD | 0.09 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000597%
European (non-Finnish) · 7/1,171,806 alleles
Filtering AF
0.000248%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00016%
Overall
0.000485%
7/1,443,460 alleles · very rare
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.Ala219=
- Coding
- c.657T>C
- MANE Select
- NM_052844
- dbSNP
- rs761447438
- Type
- single nucleotide variant
- Location
- chr9:128636327 (GRCh38)
- Gene constraint
- LOEUF 1.036 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 82.66 · 4 PDB
Similar variants
- DYNC2I2 p.Ala219Thr Uncertain significance ★★ ⚠ same residue
- 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.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-ala219 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown