DYNC2I1 p.Asp173=
c.519T>C · rs76115834 · VCV707133
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.06%, eas)
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 -1.3 | GERP -3.9 |
| Overall | ||
| CADD | 3.805 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.06%
East Asian · 471/44,272 alleles
Filtering AF
0.984%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.953%
Overall
0.0501%
793/1,582,184 alleles · low-frequency
exomes 681/1,429,972 · genomes 112/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.06% | 94 |
| Admixed American | 0.479% | 209 |
| Remaining individualsnot grpmax-eligible | 0.109% | 914 |
| Middle Eastern | 0.0167% | 5,994 |
| South Asian | 0.0095% | 10,532 |
| European (non-Finnish) | 0.000513% | 195,061 |
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.Asp173=
- Coding
- c.519T>C
- MANE Select
- NM_018051
- dbSNP
- rs76115834
- Type
- single nucleotide variant
- Location
- chr7:158876637 (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 173
- 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-asp173 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown