DYNC2H1 p.Glu3249=
c.9747G>A · rs561165138 · VCV2727584
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.066%, sas)
Conditions
1
Jeune syndrome
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 -0.082 | GERP -3, phastCons 0.089 |
| Overall | ||
| CADD | 1.554 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.066%
South Asian · 60/90,890 alleles
Filtering AF
0.0526%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0477%
Overall
0.00435%
70/1,609,898 alleles · ultra-rare
exomes 68/1,457,880 · genomes 2/152,018 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.066% | 1,515 |
| Admixed American | 0.00836% | 11,968 |
| Remaining individualsnot grpmax-eligible | 0.00642% | 15,580 |
| East Asian | 0.00224% | 44,642 |
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.Glu3249=
- Coding
- c.9747G>A
- MANE Select
- NM_001377
- dbSNP
- rs561165138
- Type
- single nucleotide variant
- Location
- chr11:103236467 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3249
- an α-helix; the 'aaa 5' 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-glu3249 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown