Is DES p.Gly75= (c.225G>A) pathogenic?

DES p.Gly75= (c.225G>A) is classified Likely benign in DES (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-07). Very rare (popmax 0.00388%, nfe); Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Gly75= (c.225G>A)?

DES p.Gly75= (c.225G>A) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Gly75= (c.225G>A) in the general population?

DES p.Gly75= (c.225G>A) is very rare (popmax 0.00388%, nfe) (gnomAD).

How is Desminopathy inherited?

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

DES p.Gly75=

c.225G>A · rs777582958 · VCV1108830

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00388%, 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 · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.64	GERP -3, phastCons 0.3
Overall
CADD	9.574	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00388% European (non-Finnish) · 45/1,159,550 alleles

Filtering AF 0.00296% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00264%

Overall 0.00292% 46/1,573,162 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00388%	25,768
South Asian	0.00116%	86,316

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.Gly75=
Coding: c.225G>A
MANE Select: NM_001927
dbSNP: rs777582958
Type: single nucleotide variant
Location: chr2:219418687 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 75: the 'head' 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.Gly75Glu 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
DES p.Ala285Val 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-gly75 (accessed [today's date]).

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