DYNC1H1 p.Leu41=
c.123G>A · rs1260546515 · VCV539797
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.0017%, amr)
Conditions
2
Charcot-Marie-Tooth disease
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 6.7 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 14.68 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0017%
Admixed American · 1/58,986 alleles
Filtering AF
0.00036%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000261%
Overall
0.000623%
10/1,604,106 alleles · very rare
exomes 9/1,451,882 · genomes 1/152,224 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0017% | 58,986 |
| European (non-Finnish) | 0.000765% | 130,732 |
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.Leu41=
- Coding
- c.123G>A
- MANE Select
- NM_001376
- dbSNP
- rs1260546515
- Type
- single nucleotide variant
- Location
- chr14:101964814 (GRCh38)
- Gene constraint
- LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 41
- 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-leu41 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown