Is DES p.Glu197del (c.586GAG[1]) pathogenic?

DES p.Glu197del (c.586GAG[1]) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-10). Very rare (popmax 0.000169%, nfe); Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Glu197del (c.586GAG[1])?

DES p.Glu197del (c.586GAG[1]) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Glu197del (c.586GAG[1]) in the general population?

DES p.Glu197del (c.586GAG[1]) is very rare (popmax 0.000169%, nfe) (gnomAD).

How is Desminopathy inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

DES p.Glu197del

c.586GAG[1] · rs1954405702 · VCV1482395

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Conditions

myofibrillar myopathy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,032 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,880 alleles · very rare

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.Glu197del
Coding: c.586GAG[1]
MANE Select: NM_001927
dbSNP: rs1954405702
Type: Microsatellite
Location: chr2:219420100 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 197: the if rod domain; the 'coil 1b' region

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

Disease context

myofibrillar myopathy 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Desminopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

DES p.Glu197= Likely benign ★ same residue
DES p.Arg163_Arg164insGluLeuArg Uncertain significance ★★ same condition
DES p.Glu373del Uncertain significance ★★ same condition
DES c.639+13_639+15del Likely benign ★★ same condition
DES p.Val176fs Pathogenic ★ same condition
DES p.Asn308del Uncertain significance ★ same condition
DES p.Asn366del Conflicting classifications of pathogenicity ★ same condition
DES p.Glu158del 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-glu197del (accessed [today's date]).

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