DES p.Thr445=
c.1335G>A · rs780984657 · VCV1084115
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00455%, sas)
Conditions
2
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 -5.8 | GERP -3.4 |
| Overall | ||
| CADD | 1.264 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00455%
South Asian · 4/87,950 alleles
Filtering AF
0.00146%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000916%
Overall
0.00075%
12/1,599,816 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00455% | 21,987 |
| Admixed American | 0.00346% | 28,898 |
| Finnishnot grpmax-eligible | 0.00158% | 63,294 |
| European (non-Finnish) | 0.000426% | 234,677 |
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.Thr445=
- Coding
- c.1335G>A
- MANE Select
- NM_001927
- dbSNP
- rs780984657
- Type
- single nucleotide variant
- Location
- chr2:219425709 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73
- Residue 445
- the 'tail' region; the 'interaction with cryab' region
Similar variants
- DES p.Thr445Ala Uncertain significance ★★ ⚠ same residue
- DES p.Thr445Met 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-thr445 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown