DYNC1H1 p.Arg3474=
c.10420C>A · VCV4923211
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0198%, sas)
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 2.1 | GERP 1.2, phastCons 1 |
| Overall | ||
| CADD | 9.456 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0198%
South Asian · 18/91,028 alleles
Filtering AF
0.0127%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0106%
Overall
0.0013%
19/1,461,568 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0198% | 5,057 |
| European (non-Finnish) | 8.47e-05% | 1,180,018 |
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.Arg3474=
- Coding
- c.10420C>A
- MANE Select
- NM_001376
- Type
- single nucleotide variant
- Location
- chr14:102033982 (GRCh38)
- Gene constraint
- LOEUF 0.117 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Residue 3474
- the 'stalk' region; an α-helix
Similar variants
- DYNC1H1 p.Arg3474Trp Pathogenic/Likely pathogenic ★★ same residue
- DYNC1H1 p.Arg3474Gln Uncertain significance ★ same residue
- DYNC1H1 p.Arg3474dup Likely pathogenic ★ same residue
- DYNC1H1 c.4396-1G>C Likely pathogenic ★★ same type
- DYNC1H1 p.Ala4519Val Likely pathogenic ★★ same type
- DYNC1H1 p.Arg1567Gln Pathogenic/Likely pathogenic ★★ same type
- DYNC1H1 p.Arg1623Gln Pathogenic/Likely pathogenic ★★ same type
- DYNC1H1 p.Arg1623Trp Pathogenic ★★ same type
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-arg3474 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown