DYNC2H1 p.Glu3473=
c.10419G>A · rs374923463 · VCV2891154
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0241%, afr)
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 -0.27 | GERP -3.6, phastCons 0.047 |
| Overall | ||
| CADD | 2.459 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0241%
African / African-American · 18/74,732 alleles
Filtering AF
0.0155%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0129%
Overall
0.00124%
20/1,606,440 alleles · ultra-rare
exomes 8/1,454,314 · genomes 12/152,126 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0241% | 4,152 |
| Remaining individualsnot grpmax-eligible | 0.00322% | 31,097 |
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.Glu3473=
- Coding
- c.10419G>A
- MANE Select
- NM_001377
- dbSNP
- rs374923463
- Type
- single nucleotide variant
- Location
- chr11:103256198 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 3473
- 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-glu3473 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown