Is DES p.Ala120= (c.360C>T) pathogenic?

DES p.Ala120= (c.360C>T) is classified Likely benign in DES (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-05-19). No allele count reported in gnomAD v4.1 (AN 1,579,966); Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Ala120= (c.360C>T)?

DES p.Ala120= (c.360C>T) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Ala120= (c.360C>T) in the general population?

DES p.Ala120= (c.360C>T) is no allele count reported in gnomAD v4.1 (AN 1,579,966) (gnomAD).

How is Desminopathy inherited?

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

DES p.Ala120=

c.360C>T · rs1553603246 · VCV541309

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,579,966)

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 3.2	GERP -0.46, phastCons 1
Overall
CADD	14.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,579,966). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: DES
Protein: p.Ala120=
Coding: c.360C>T
MANE Select: NM_001927
dbSNP: rs1553603246
Type: single nucleotide variant
Location: chr2:219418822 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 120: the if rod domain; the 'coil 1a' region; a UniProt-annotated variant site (in cmd1i; results in impaired filaments formation, does not localize at intercalated disks)

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.Ala120Pro Pathogenic/Likely pathogenic ★★ same residue
DES p.Ala120Gly Uncertain significance ★★ ⚠ same residue
DES p.Ala120Asp Likely pathogenic ★ 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

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-ala120 (accessed [today's date]).

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