Is DES p.Arg406= (c.1218G>C) pathogenic?

DES p.Arg406= (c.1218G>C) is classified Likely benign in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-19). Absent from gnomAD v4.1; Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Arg406= (c.1218G>C)?

DES p.Arg406= (c.1218G>C) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Arg406= (c.1218G>C) in the general population?

DES p.Arg406= (c.1218G>C) is absent from gnomAD v4.1 (gnomAD).

How is Desminopathy inherited?

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

DES p.Arg406=

c.1218G>C · rs2545255464 · VCV2928759

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.3	GERP 0.72, phastCons 1
Overall
CADD	13.84	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.Arg406=
Coding: c.1218G>C
MANE Select: NM_001927
dbSNP: rs2545255464
Type: single nucleotide variant
Location: chr2:219421534 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 406: the 'coil 2b' region; the if rod domain; a UniProt-annotated variant site (in mfm1; unable to form a filamentous network); the 'interaction with neb' 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.Arg406Trp Pathogenic/Likely pathogenic ★★ same residue
DES p.Arg406Pro Likely pathogenic ★ same residue
DES p.Arg406Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
DES p.Arg406Leu 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-arg406 (accessed [today's date]).

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