Is DES p.Glu108Ter (c.322G>T) pathogenic?

DES p.Glu108Ter (c.322G>T) is classified Conflicting classifications of pathogenicity in DES (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-06-25). Very rare (popmax 0.00121%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Glu108Ter (c.322G>T)?

DES p.Glu108Ter (c.322G>T) is associated with Cardiovascular phenotype, neurogenic scapuloperoneal syndrome, Kaeser type, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Glu108Ter (c.322G>T) in the general population?

DES p.Glu108Ter (c.322G>T) is very rare (popmax 0.00121%, nfe) (gnomAD).

DES p.Glu108Ter

c.322G>T · rs62636490 · VCV804737

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00121%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Overall
CADD	44.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00121% European (non-Finnish) · 14/1,154,742 alleles

Filtering AF 0.000704% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00055%

Overall 0.000894% 14/1,566,156 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.Glu108Ter
Coding: c.322G>T
MANE Select: NM_001927
dbSNP: rs62636490
Type: single nucleotide variant
Location: chr2:219418784 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 108: the if rod domain; the 'head' 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.Glu108Gly Uncertain significance ★★ ⚠ same residue
DES p.Glu108= Benign/Likely benign ★★ same residue
DES p.Glu108Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
DES p.Glu108fs 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

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-glu108ter (accessed [today's date]).

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