DNM2 p.Pro405=
c.1215C>T · rs546498406 · VCV2498752
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0535%, eas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.40 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.9 | GERP -3.7 |
| Overall | ||
| CADD | 9.295 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0535%
East Asian · 24/44,876 alleles
Filtering AF
0.0368%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0313%
Overall
0.0118%
191/1,613,118 alleles · ultra-rare
exomes 182/1,460,912 · genomes 9/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0535% | 1,870 |
| European (non-Finnish) | 0.0133% | 7,516 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,487 |
| Admixed American | 0.00333% | 29,994 |
| African / African-American | 0.00267% | 37,477 |
| South Asian | 0.0011% | 91,008 |
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
- DNM2
- Protein
- p.Pro405=
- Coding
- c.1215C>T
- MANE Select
- NM_001005361
- dbSNP
- rs546498406
- Type
- single nucleotide variant
- Location
- chr19:10797398 (GRCh38)
- Gene constraint
- LOEUF 0.239 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.38 · 1 PDB
Similar variants
- DNM2 p.Ala618Thr Pathogenic ★★★ same type
- DNM2 p.Arg369Gln Pathogenic ★★★ ⚠ same type
- DNM2 p.Arg369Trp Pathogenic ★★★ same type
- DNM2 p.Arg465Trp Pathogenic ★★★ same type
- DNM2 p.Arg522Cys Likely pathogenic ★★★ same type
- DNM2 p.Arg522His Pathogenic ★★★ same type
- DNM2 p.Arg523Gly Likely pathogenic ★★★ same type
- DNM2 p.Asp614Asn Likely 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/dnm2-p-pro405 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown