DYNC2I1 p.Glu100=
c.300G>A · rs573590917 · VCV2978617
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0503%, mid)
Conditions
1
short-rib thoracic dysplasia 8 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 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.32 | GERP -3.3, phastCons 0.41 |
| Overall | ||
| CADD | 5.507 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0503%
Middle Eastern · 3/5,968 alleles
Filtering AF
0.0136%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00729%
Overall
0.00265%
41/1,548,538 alleles · ultra-rare
exomes 39/1,399,864 · genomes 2/148,674 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0503% | 1,989 |
| Remaining individualsnot grpmax-eligible | 0.00332% | 30,080 |
| European (non-Finnish) | 0.00306% | 32,716 |
| Admixed American | 0.00197% | 50,762 |
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
- DYNC2I1
- Protein
- p.Glu100=
- Coding
- c.300G>A
- MANE Select
- NM_018051
- dbSNP
- rs573590917
- Type
- single nucleotide variant
- Location
- chr7:158871372 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 62.87 · 4 PDB
- Residue 100
- the 'disordered' region
Similar variants
- DYNC2I1 p.Arg228Ter Pathogenic/Likely pathogenic ★★ same condition
- DYNC2I1 p.Arg441Ter Pathogenic/Likely pathogenic ★★ same condition
- DYNC2I1 p.Arg642Ter Pathogenic/Likely pathogenic ★★ same condition
- DYNC2I1 p.Arg762Ter Pathogenic ★★ same condition
- DYNC2I1 p.Ala157Val Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Ala609Val Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Ala800Thr Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Ala822Thr 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/dync2i1-p-glu100 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown