DES p.Leu74=
c.222G>A · VCV4239719
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00232%, eas)
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 7.2 | GERP 0.51, phastCons 1 |
| Overall | ||
| CADD | 14.33 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00232%
East Asian · 1/43,112 alleles
Overall
6.35e-05%
1/1,575,158 alleles · very rare
exomes 1/1,423,040 · genomes 0/152,118 · joint denominator
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.Leu74=
- Coding
- c.222G>A
- MANE Select
- NM_001927
- Type
- single nucleotide variant
- Location
- chr2:219418684 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73
- Residue 74
- the 'head' region
Similar variants
- DES p.Leu74Pro Uncertain significance ★ ⚠ same residue
- DES p.Leu74Gln Uncertain significance ★ ⚠ same residue
- DES p.Arg212Ter Pathogenic/Likely pathogenic ★★ same condition
- DES p.Arg454Trp 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
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-leu74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown