Is DES p.Glu230= (c.690A>G) pathogenic?

DES p.Glu230= (c.690A>G) is classified Likely benign in DES (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-20). Ultra-rare (popmax 0.0669%, eas); Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Glu230= (c.690A>G)?

DES p.Glu230= (c.690A>G) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Glu230= (c.690A>G) in the general population?

DES p.Glu230= (c.690A>G) is ultra-rare (popmax 0.0669%, eas) (gnomAD).

How is Desminopathy inherited?

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

DES p.Glu230=

c.690A>G · rs142145822 · VCV724815

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0669%, eas)

Conditions

myofibrillar myopathy 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.44	GERP -3.7, phastCons 0.8
Overall
CADD	9.424	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0669% East Asian · 30/44,862 alleles

Filtering AF 0.0481% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0417%

Overall 0.00192% 31/1,614,140 alleles · ultra-rare exomes 29/1,461,892 · genomes 2/152,248 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0669%	1,495
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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.Glu230=
Coding: c.690A>G
MANE Select: NM_001927
dbSNP: rs142145822
Type: single nucleotide variant
Location: chr2:219420301 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 230: 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 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
DES p.Ala285Val Likely pathogenic ★★ same condition
DES p.Arg212Ter 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-glu230 (accessed [today's date]).

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