DYNC2I1 p.Val660Ile
c.1978G>A · VCV4245847
Computational evidence
| Protein change | ||
| AlphaMissense | 0.094 | likely benign |
|---|---|---|
| REVEL | 0.287 | benign-leaning |
| SaProt | LLR -7.57 | tolerated |
| ⇒ AlphaMissense, REVEL and SaProt all call this tolerated. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 8.3 | GERP 1.1, phastCons 1 |
| Regional constraint | o/e 0.98 | unconstrained · MANE · 89 kb · p 0.52 · regional, not allelic |
| Overall | ||
| CADD | 20.9 | PHRED · no single calibrated threshold — expert panels disagree |
ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.115% | 869 |
| Admixed American | 0.00333% | 29,999 |
| European (non-Finnish) | 0.00237% | 42,140 |
| African / African-American | 0.00134% | 74,900 |
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.Val660Ile
- Coding
- c.1978G>A
- MANE Select
- NM_018051
- Type
- single nucleotide variant
- Location
- chr7:158922433 (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 660
- a UniProt-annotated variant site (in srtd8; reduces interaction with ift proteins); a UniProt-annotated variant site (in srtd8)
Similar variants
- DYNC2I1 p.Ala157Val Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Ala822Thr Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Ala956Val Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Arg1038Trp Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Arg109Gln Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Arg149Cys Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Arg162Leu Uncertain significance ★★ ⚠ same condition
- DYNC2I1 p.Arg319Gly 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-val660ile (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown