DES p.Glu245=
c.735G>A · rs267607486 · VCV281234
Conflicting classifications of pathogenicity
Conflicting submitters
Classification
Conflicting classifications of pathogenicity
ClinVar
Review
Conflicting submitters ★☆☆☆
ClinVar · 5 submitters
gnomAD v4.1
Absent
absent from gnomAD v4.1
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.30 | donor gain · deltas |
|---|---|---|
| Pangolin | Δ0.71 | loss · gain 0.24 · SpliceAI calls gain · independent |
| Constraint at this position | ||
| Conservation | phyloP 12 | GERP 1.9, phastCons 1 |
| Overall | ||
| CADD | 23.5 | 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.Glu245=
- Coding
- c.735G>A
- MANE Select
- NM_001927
- dbSNP
- rs267607486
- Type
- single nucleotide variant
- Location
- chr2:219420346 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73
- Residue 245
- the if rod domain; a UniProt-annotated variant site (in mfm1; exhibits significantly delayed filament assembly kinetics when bound to neb and nebl; enhanced binding affinity towards neb and nebl); the 'coil 1b' region
Similar variants
- DES p.Glu245Asp Pathogenic/Likely pathogenic ★★ ⚠ same residue
- DES p.Glu245Gly Uncertain significance ★ ⚠ same residue
- DES c.1289-2A>G Pathogenic/Likely pathogenic ★★ same condition
- DES c.579-2A>C Likely pathogenic ★★ same condition
- DES c.735+1G>A Pathogenic/Likely pathogenic ★★ same condition
- DES c.735+1G>C Pathogenic/Likely pathogenic ★★ same condition
- DES c.735+3A>G Pathogenic ★★ same condition
- DES p.Ala120Pro Pathogenic/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/des-p-glu245 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown