DYNC1H1 p.Arg4092=
c.12276G>A · rs746372351 · VCV1159817
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0617%, amr)
Conditions
2
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.45 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 6.6 | GERP 1.1, phastCons 1 |
| Overall | ||
| CADD | 21.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0617%
Admixed American · 37/60,000 alleles
Filtering AF
0.0459%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0405%
Overall
0.00285%
46/1,614,082 alleles · ultra-rare
exomes 44/1,461,886 · genomes 2/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0617% | 1,622 |
| South Asian | 0.00329% | 30,365 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,490 |
| African / African-American | 0.00133% | 74,934 |
| European (non-Finnish) | 0.000339% | 295,014 |
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
- DYNC1H1
- Protein
- p.Arg4092=
- Coding
- c.12276G>A
- MANE Select
- NM_001376
- dbSNP
- rs746372351
- Type
- single nucleotide variant
- Location
- chr14:102042384 (GRCh38)
- Gene constraint
- LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 4092
- the 'aaa 6' region
Similar variants
- DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same condition
- DYNC1H1 p.Arg1623Gln Pathogenic/Likely pathogenic ★★ same condition
- DYNC1H1 p.Arg1962Cys Pathogenic ★★ same condition
- DYNC1H1 p.Arg1962His Likely pathogenic ★★ same condition
- DYNC1H1 p.Arg2332Cys Pathogenic/Likely pathogenic ★★ same condition
- DYNC1H1 p.Arg251Ser Pathogenic/Likely pathogenic ★★ same condition
- DYNC1H1 p.Arg264Leu Pathogenic ★★ same condition
- DYNC1H1 p.Arg292Trp 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/dync1h1-p-arg4092 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown