Is DES p.Ala71= (c.213C>T) pathogenic?

DES p.Ala71= (c.213C>T) is classified Likely benign in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). Very rare (popmax 0.000172%, nfe); Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Ala71= (c.213C>T)?

DES p.Ala71= (c.213C>T) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Ala71= (c.213C>T) in the general population?

DES p.Ala71= (c.213C>T) is very rare (popmax 0.000172%, nfe) (gnomAD).

How is Desminopathy inherited?

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

DES p.Ala71=

c.213C>T · rs2545246620 · VCV2186580

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000172%, 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 1.3	GERP 0.66, phastCons 1
Overall
CADD	14.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000172% European (non-Finnish) · 2/1,163,012 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00014% 2/1,427,226 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.Ala71=
Coding: c.213C>T
MANE Select: NM_001927
dbSNP: rs2545246620
Type: single nucleotide variant
Location: chr2:219418675 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 71: 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.Ala71Gly Uncertain significance ★★ ⚠ same residue
DES p.Ala71Val Uncertain significance ★★ ⚠ same residue
DES p.Ala71Ser 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

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-ala71 (accessed [today's date]).

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