Is DES p.Asn308= (c.924C>T) pathogenic?

DES p.Asn308= (c.924C>T) is classified Conflicting classifications of pathogenicity in DES (ClinVar, Conflicting submitters, 11 submitters; last evaluated 2026-01-26). Rare (popmax 0.239%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Asn308= (c.924C>T)?

DES p.Asn308= (c.924C>T) is associated with Cardiovascular phenotype, neurogenic scapuloperoneal syndrome, Kaeser type, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Asn308= (c.924C>T) in the general population?

DES p.Asn308= (c.924C>T) is rare (popmax 0.239%, sas) (gnomAD).

DES p.Asn308=

c.924C>T · rs578191306 · VCV283467

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 11 submitters

gnomAD v4.1

Rare

rare (popmax 0.239%, sas)

Conditions

Cardiovascular phenotype

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 0.016	GERP -0.41, phastCons 0.81
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.239% South Asian · 218/91,070 alleles

Filtering AF 0.213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.203%

Overall 0.0152% 246/1,613,808 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.239%	418
Remaining individualsnot grpmax-eligible	0.0176%	5,682
Middle Eastern	0.0165%	6,062
East Asian	0.00223%	44,852
European (non-Finnish)	0.00127%	78,667

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.Asn308=
Coding: c.924C>T
MANE Select: NM_001927
dbSNP: rs578191306
Type: single nucleotide variant
Location: chr2:219420854 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 308: the 'coil 2b' region; the if rod domain; the 'interaction with neb' region

Full DES gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: neurogenic scapuloperoneal syndrome, Kaeser type myofibrillar myopathy 1 dilated cardiomyopathy 1I

Similar variants

DES p.Asn308Lys Uncertain significance ★★ ⚠ same residue
DES p.Asn308His Uncertain significance ★ ⚠ same residue
DES p.Asn308Ser Uncertain significance ★ ⚠ same residue
DES p.Asn308del 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-asn308 (accessed [today's date]).

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