DYNC2I1 p.Leu592=
c.1776G>A · rs2536245743 · VCV2818020
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
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 -2.5 | GERP -3.4 |
| Overall | ||
| CADD | 0.704 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,178,740 alleles
Overall
6.21e-05%
1/1,611,570 alleles · very rare
exomes 1/1,459,300 · genomes 0/152,270 · joint denominator
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.Leu592=
- Coding
- c.1776G>A
- MANE Select
- NM_018051
- dbSNP
- rs2536245743
- Type
- single nucleotide variant
- Location
- chr7:158914306 (GRCh38)
- Gene constraint
- LOEUF 0.802 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 62.87 · 4 PDB
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-leu592 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown