DNM1L p.Arg263Ser
c.787C>A · VCV4723037
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
AlphaMissense
likely pathogenic
0.6231 · ACMG-weighted
gnomAD v4.1
Absent
absent from gnomAD v4.1
Missense predictors
1/2 damaging
AlphaMissense, SaProt · REVEL no call
Computational evidence
| Protein change | ||
| AlphaMissense | 0.6231 | likely pathogenic |
|---|---|---|
| REVEL | 0.414 | indeterminate |
| SaProt | LLR -8.64 | tolerated |
| ⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.1 | phastCons 0.99 |
| Regional constraint | o/e 0.58 | unconstrained · MANE · 19 kb · p 1.9e-12 · regional, not allelic |
| Overall | ||
| CADD | 26.8 | PHRED · no single calibrated threshold — expert panels disagree |
AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- DNM1L
- Protein
- p.Arg263Ser
- Coding
- c.787C>A
- MANE Select
- NM_012062
- Type
- single nucleotide variant
- Location
- chr12:32720710 (GRCh38)
- Gene constraint
- LOEUF 0.506 · pLI 0.92 (gnomAD)
- Structure
- AlphaFold pLDDT 77.09 · 11 PDB
- Residue 263
- the dynamin-type g domain; an α-helix
Similar variants
- DNM1L p.Arg263Cys Uncertain significance ★ ⚠ same residue
- DNM1L p.Arg263His Uncertain significance ★ ⚠ same residue
- DNM1L p.Arg263Pro Uncertain significance ★ ⚠ same residue
- 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
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-arg263ser (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown