DYNC1H1 p.Leu4265=
c.12795C>T · rs371160908 · VCV390544
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0386%, afr)
Conditions
2
Inborn genetic diseases
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 0.46 | GERP -1.1, phastCons 0.99 |
| Overall | ||
| CADD | 16.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0386%
African / African-American · 29/75,058 alleles
Filtering AF
0.0276%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0238%
Overall
0.00279%
45/1,614,156 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0386% | 2,588 |
| Admixed American | 0.0233% | 4,287 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,510 |
| South Asian | 0.0011% | 91,080 |
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.Leu4265=
- Coding
- c.12795C>T
- MANE Select
- NM_001376
- dbSNP
- rs371160908
- Type
- single nucleotide variant
- Location
- chr14:102044384 (GRCh38)
- Gene constraint
- LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 4265
- an α-helix
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-leu4265 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown