DYNC2H1 p.Leu2019=
c.6057A>G · rs187190605 · VCV389980
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0434%, amr)
Conditions
1
Jeune syndrome
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.37 | acceptor loss, 2 bp away · masked 0 · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 2.1 | GERP 0.41, phastCons 1 |
| Overall | ||
| CADD | 6.608 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0434%
Admixed American · 26/59,930 alleles
Filtering AF
0.0304%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.026%
Overall
0.00713%
115/1,613,508 alleles · ultra-rare
exomes 97/1,461,238 · genomes 18/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0434% | 2,305 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0237% | 4,227 |
| Remaining individualsnot grpmax-eligible | 0.0176% | 5,679 |
| Middle Eastern | 0.0165% | 6,058 |
| European (non-Finnish) | 0.00585% | 17,097 |
| African / African-American | 0.00133% | 75,034 |
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
- DYNC2H1
- Protein
- p.Leu2019=
- Coding
- c.6057A>G
- MANE Select
- NM_001377
- dbSNP
- rs187190605
- Type
- single nucleotide variant
- Location
- chr11:103177738 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 2019
- an α-helix; the 'aaa 2' region
Similar variants
- DYNC2H1 c.10042+2T>G Pathogenic/Likely pathogenic ★★ same condition
- DYNC2H1 c.10462-2A>G Likely pathogenic ★★ same condition
- DYNC2H1 c.10606-14A>G Pathogenic/Likely pathogenic ★★ same condition
- DYNC2H1 c.10695+1G>A Likely pathogenic ★★ same condition
- DYNC2H1 c.10813-2A>G Likely pathogenic ★★ same condition
- DYNC2H1 c.11493+2T>A Likely pathogenic ★★ same condition
- DYNC2H1 c.11650-1G>A Pathogenic/Likely pathogenic ★★ same condition
- DYNC2H1 c.12457-1G>C Likely pathogenic ★★ 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/dync2h1-p-leu2019 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown