Is DES p.Asn233= (c.699C>T) pathogenic?

DES p.Asn233= (c.699C>T) is classified Benign/Likely benign in DES (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-05-10). Ultra-rare (popmax 0.0227%, afr); Associated with myofibrillar myopathy 1.

What condition is associated with DES p.Asn233= (c.699C>T)?

DES p.Asn233= (c.699C>T) is associated with myofibrillar myopathy 1 (ClinVar).

How common is DES p.Asn233= (c.699C>T) in the general population?

DES p.Asn233= (c.699C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

How is Desminopathy inherited?

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

DES p.Asn233=

c.699C>T · rs758066814 · VCV416614

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

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 -8.7	GERP -3.7
Overall
CADD	10.87	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/74,906 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00198% 32/1,614,070 alleles · ultra-rare exomes 19/1,461,878 · genomes 13/152,192 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,406
Remaining individualsnot grpmax-eligible	0.008%	12,497
East Asian	0.00223%	44,892
European (non-Finnish)	0.000763%	131,117

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.Asn233=
Coding: c.699C>T
MANE Select: NM_001927
dbSNP: rs758066814
Type: single nucleotide variant
Location: chr2:219420310 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 233: 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 p.Asn233Lys 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-asn233 (accessed [today's date]).

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