Is DES p.Arg436fs (c.1306del) pathogenic?

DES p.Arg436fs (c.1306del) is classified Uncertain significance in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-26). Absent from gnomAD; Associated with Cardiovascular phenotype.

What condition is associated with DES p.Arg436fs (c.1306del)?

DES p.Arg436fs (c.1306del) is associated with Cardiovascular phenotype (ClinVar).

How common is DES p.Arg436fs (c.1306del) in the general population?

DES p.Arg436fs (c.1306del) is absent from gnomAD (gnomAD).

DES p.Arg436fs

c.1306del · rs2545263585 · VCV3221928

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 9
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.6	GERP 1.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Arg436fs
Coding: c.1306del
MANE Select: NM_001927
dbSNP: rs2545263585
Type: Deletion
Location: chr2:219425678 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 436: the 'tail' 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

Similar variants

DES p.Arg436Ser Uncertain significance ★★ same residue
DES p.Arg436= Likely benign ★ same residue
DES p.Glu179_Leu184del Uncertain significance ★★ same condition
DES p.Lys449_Ile451del Uncertain significance ★★ same condition
DES c.897+4_897+5del Benign/Likely benign ★★ same condition
DES c.638_639+5del Uncertain significance ★ same condition
DES p.Asp181_Leu184delinsVal Uncertain significance ★ same condition
DES p.Asp455fs Uncertain significance ★ 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-arg436fs (accessed [today's date]).

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