DYNC2LI1 p.Ala333Pro
c.997G>C · rs186836054 · VCV3035780
Benign
No assertion criteria
Classification
Benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.02%, eas)
Conditions
1
DYNC2LI1-related disorder
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 1.1 | GERP -2, phastCons 0.032 |
| Overall | ||
| CADD | 7.303 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.02%
East Asian · 90/8,810 alleles
Filtering AF
0.851%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.788%
Overall
0.0127%
125/985,270 alleles · low-frequency
exomes 63/833,056 · genomes 62/152,214 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 1.02% | 98 |
| Remaining individualsnot grpmax-eligible | 0.0748% | 1,337 |
| South Asian | 0.047% | 2,127 |
| Admixed American | 0.00615% | 16,272 |
| African / African-American | 0.00174% | 57,320 |
| European (non-Finnish) | 0.000121% | 829,869 |
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.Ala333Pro
- Coding
- c.997G>C
- MANE Select
- NM_016008 · reported on NM_001348913
- dbSNP
- rs186836054
- Type
- single nucleotide variant
- Location
- chr2:43810381 (GRCh38)
- Gene constraint
- LOEUF 1.028 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 85.49 · 3 PDB
Disease context
DYNC2LI1-related disorder
Similar variants
- DYNC2LI1 p.Leu117Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
- DYNC2LI1 p.Leu62Ter Likely pathogenic ★ same condition
- ABCG5 p.Thr305= Conflicting classifications of pathogenicity ★ same condition
- DYNC2LI1 c.162-10_162-2delinsAG Likely pathogenic ★ same condition
- DYNC2LI1 p.Leu280fs Likely pathogenic ★ same condition
- DYNC2LI1 p.Trp124Ter Pathogenic/Likely pathogenic ★★ same type
- ABCG5 p.Ala505Asp Uncertain significance ★★ ⚠ same type
- ABCG5 p.Gly288Ser 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-ala333pro (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown