DNM2 p.Lys577=
c.1731G>A · rs35365412 · VCV158516
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
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 2.9 | GERP -2, phastCons 1 |
| Overall | ||
| CADD | 8.418 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,028 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000496%
8/1,614,186 alleles · very rare
exomes 8/1,461,878 · genomes 0/152,308 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,009 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,512 |
| European (non-Finnish) | 0.000339% | 295,008 |
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.Lys577=
- Coding
- c.1731G>A
- MANE Select
- NM_001005361
- dbSNP
- rs35365412
- Type
- single nucleotide variant
- Location
- chr19:10820039 (GRCh38)
- Gene constraint
- LOEUF 0.239 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 78.38 · 1 PDB
- Residue 577
- the ph domain
Similar variants
- DNM2 p.Lys577Asn Uncertain significance ★ ⚠ same residue
- DNM2 p.Ala618Thr Pathogenic ★★★ same condition
- DNM2 p.Arg369Gln Pathogenic ★★★ ⚠ same condition
- DNM2 p.Arg369Trp Pathogenic ★★★ same condition
- DNM2 p.Arg465Trp Pathogenic ★★★ same condition
- DNM2 p.Arg522Cys Likely pathogenic ★★★ same condition
- DNM2 p.Arg522His Pathogenic ★★★ same condition
- DNM2 p.Arg523Gly Likely 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/dnm2-p-lys577 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown