DES p.Val458=
c.1374C>T · rs727502952 · VCV163029
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0604%, sas)
Conditions
2
Cardiovascular phenotype
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · C>A here scores Δ0.37 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.5 | GERP -2.9 |
| Overall | ||
| CADD | 6.118 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0604%
South Asian · 55/91,074 alleles
Filtering AF
0.0476%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.043%
Overall
0.00378%
61/1,613,888 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0604% | 1,656 |
| European (non-Finnish) | 0.000508% | 196,667 |
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
- DES
- Protein
- p.Val458=
- Coding
- c.1374C>T
- MANE Select
- NM_001927
- dbSNP
- rs727502952
- Type
- single nucleotide variant
- Location
- chr2:219425951 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73
- Residue 458
- the 'tail' region
Similar variants
- 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
- DES p.Ala285Val Likely pathogenic ★★ same condition
- DES p.Arg212Ter 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-val458 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown