DNM1L p.Leu289=
c.867A>G · rs891531486 · VCV1622470
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0214%, afr)
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 1.6 | phastCons 1 |
| Overall | ||
| CADD | 6.725 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0214%
African / African-American · 16/74,902 alleles
Filtering AF
0.0133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0109%
Overall
0.00136%
22/1,613,000 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0214% | 4,681 |
| Remaining individualsnot grpmax-eligible | 0.00641% | 15,597 |
| Admixed American | 0.00333% | 29,992 |
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
- DNM1L
- Protein
- p.Leu289=
- Coding
- c.867A>G
- MANE Select
- NM_012062
- dbSNP
- rs891531486
- Type
- single nucleotide variant
- Location
- chr12:32720790 (GRCh38)
- Gene constraint
- LOEUF 0.506 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 77.09 · 11 PDB
- Residue 289
- the dynamin-type g domain; an α-helix
Similar variants
- DNM1L c.1596+2T>A Likely pathogenic ★★ same type
- DNM1L c.1674+1G>A Pathogenic/Likely pathogenic ★★ same type
- DNM1L p.Arg403Cys Pathogenic ★★ same type
- DNM1L p.Arg530Ter Pathogenic/Likely pathogenic ★★ same type
- DNM1L p.Asp146Asn Pathogenic/Likely pathogenic ★★ ⚠ same type
- DNM1L p.Cys431Tyr Pathogenic ★★ same type
- DNM1L p.Gly362Ser Pathogenic ★★ same type
- DNM1L p.Gly401Ser 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/dnm1l-p-leu289 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown