DYNC2H1 p.Pro4263=
c.12789G>A · rs371957414 · VCV2642331
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0312%, eas)
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 -5.4 | GERP -3.2 |
| Overall | ||
| CADD | 1.771 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0312%
East Asian · 14/44,858 alleles
Filtering AF
0.0188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0151%
Overall
0.00521%
84/1,613,534 alleles · ultra-rare
exomes 78/1,461,568 · genomes 6/151,966 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0312% | 3,204 |
| Finnishnot grpmax-eligible | 0.0235% | 4,263 |
| South Asian | 0.0231% | 4,336 |
| Remaining individualsnot grpmax-eligible | 0.0048% | 20,826 |
| European (non-Finnish) | 0.00263% | 38,054 |
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.Pro4263=
- Coding
- c.12789G>A
- MANE Select
- NM_001377
- dbSNP
- rs371957414
- Type
- single nucleotide variant
- Location
- chr11:103479118 (GRCh38)
- Gene constraint
- LOEUF 0.859 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 4263
- a turn
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-pro4263 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown