Is DES p.Arg15= (c.45C>T) pathogenic?

DES p.Arg15= (c.45C>T) is classified Likely benign in DES (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-22). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DES p.Arg15= (c.45C>T)?

DES p.Arg15= (c.45C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Arg15= (c.45C>T) in the general population?

DES p.Arg15= (c.45C>T) is absent from gnomAD v4.1 (gnomAD).

DES p.Arg15=

c.45C>T · rs1575012917 · VCV797828

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

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 4	GERP 0.5, phastCons 1
Overall
CADD	15.76	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.Arg15=
Coding: c.45C>T
MANE Select: NM_001927
dbSNP: rs1575012917
Type: single nucleotide variant
Location: chr2:219418507 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 15: the 'head' region

Full DES gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: myofibrillar myopathy 1

Similar variants

DES p.Arg15Ser Uncertain significance ★★ ⚠ same residue
DES p.Arg15Cys Uncertain significance ★ ⚠ same residue
DES p.Arg15Gly Uncertain significance ★ ⚠ same residue
DES p.Arg15Pro 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

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-arg15 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown