DES p.Arg454=
c.1360C>A · rs267607490 · VCV1770828
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
1
Cardiovascular phenotype
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 3.2 | GERP 1.7, phastCons 1 |
| Overall | ||
| CADD | 12.9 | PHRED · no single calibrated threshold — expert panels disagree |
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
- DES
- Protein
- p.Arg454=
- Coding
- c.1360C>A
- MANE Select
- NM_001927
- dbSNP
- rs267607490
- Type
- single nucleotide variant
- Location
- chr2:219425734 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73
- Residue 454
- the 'tail' region; a UniProt-annotated variant site (in mfm1; reveals a severe disturbance of filament-formation competence and filament-filament interactions; increased interaction with cryab)
Similar variants
- DES p.Arg454Trp Pathogenic/Likely pathogenic ★★ same residue
- DES p.Arg454Gln Uncertain significance ★★ ⚠ same residue
- DES p.Arg212Ter Pathogenic/Likely pathogenic ★★ same condition
- DES p.Glu401Asp Pathogenic/Likely pathogenic ★★ same condition
- DES c.1245-3T>G Uncertain significance ★★ same condition
- DES c.639+4A>G Uncertain significance ★★ same condition
- DES p.Ala135Gly Uncertain significance ★★ ⚠ same condition
- DES p.Ala137Val Uncertain significance ★★ ⚠ 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/des-p-arg454 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown