DES p.Pro148=
c.444G>A · rs767505861 · VCV1146819
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 4 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000693%, nfe)
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 -1 | GERP -3.7 |
| Overall | ||
| CADD | 8.517 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000693%
European (non-Finnish) · 8/1,153,938 alleles
Filtering AF
0.000298%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000216%
Overall
0.000512%
8/1,563,486 alleles · very rare
exomes 7/1,411,244 · genomes 1/152,242 · 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.Pro148=
- Coding
- c.444G>A
- MANE Select
- NM_001927
- dbSNP
- rs767505861
- Type
- single nucleotide variant
- Location
- chr2:219418906 (GRCh38)
- Gene constraint
- LOEUF 0.81 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 77.73
- Residue 148
- the if rod domain; the 'linker 1' region
Similar variants
- DES p.Pro148Leu Uncertain significance ★★ ⚠ same residue
- DES p.Pro148Gln 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-pro148 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown