DYNC2LI1 p.Pro254=
c.762G>A · rs145754782 · VCV783328
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.171%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.008 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP 0.68 | GERP -1.9, phastCons 0.95 |
| Overall | ||
| CADD | 9.329 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.171%
African / African-American · 128/74,866 alleles
Filtering AF
0.147%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.138%
Overall
0.0117%
189/1,609,602 alleles · rare
exomes 112/1,457,518 · genomes 77/152,084 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.171% | 585 |
| East Asian | 0.0268% | 3,728 |
| Remaining individualsnot grpmax-eligible | 0.0257% | 3,895 |
| Admixed American | 0.0252% | 3,969 |
| South Asian | 0.00666% | 15,025 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00339% | 29,522 |
| Finnishnot grpmax-eligible | 0.00157% | 63,882 |
| European (non-Finnish) | 0.000849% | 117,767 |
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
- DYNC2LI1
- Protein
- p.Pro254=
- Coding
- c.762G>A
- MANE Select
- NM_016008
- dbSNP
- rs145754782
- Type
- single nucleotide variant
- Location
- chr2:43801669 (GRCh38)
- Gene constraint
- LOEUF 1.028 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.49 · 3 PDB
Similar variants
- DYNC2LI1 p.Pro254Leu Uncertain significance ★★ ⚠ same residue
- DYNC2LI1 p.Pro254Ser Uncertain significance ★ ⚠ same residue
- DYNC2LI1 p.Leu117Val Pathogenic/Likely pathogenic ★★ ⚠ same type
- DYNC2LI1 p.Trp124Ter Pathogenic/Likely pathogenic ★★ same type
- ABCG5 p.Ala505Asp Uncertain significance ★★ ⚠ same type
- ABCG5 p.Gly288Ser Uncertain significance ★★ ⚠ same type
- ABCG5 p.Ser361Cys Uncertain significance ★★ ⚠ same type
- ABCG5 p.Val420Gly Uncertain significance ★★ ⚠ same type
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/dync2li1-p-pro254 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown