Is DES p.Arg163= (c.489G>A) pathogenic?

DES p.Arg163= (c.489G>A) is classified Likely benign in DES (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-03-31). Very rare (popmax 0.00322%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Arg163= (c.489G>A)?

DES p.Arg163= (c.489G>A) is associated with Cardiovascular phenotype, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Arg163= (c.489G>A) in the general population?

DES p.Arg163= (c.489G>A) is very rare (popmax 0.00322%, nfe) (gnomAD).

DES p.Arg163=

c.489G>A · rs1448975712 · VCV700187

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00322%, nfe)

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 4.9	GERP -3.7, phastCons 1
Overall
CADD	15.81	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00322% European (non-Finnish) · 37/1,149,776 alleles

Filtering AF 0.00237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00238% 37/1,555,654 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.Arg163=
Coding: c.489G>A
MANE Select: NM_001927
dbSNP: rs1448975712
Type: single nucleotide variant
Location: chr2:219418951 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 163: the if rod domain; the 'coil 1b' 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: myofibrillar myopathy 1

Similar variants

DES p.Arg163Gln Uncertain significance ★★ ⚠ same residue
DES p.Arg163Pro Uncertain significance ★★ ⚠ same residue
DES p.Arg163_Arg164insGluLeuArg Uncertain significance ★★ same residue
DES p.Arg163_Arg164insGlnLeuArg Uncertain significance ★ same residue
DES p.Arg163_Val168dup 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

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-arg163 (accessed [today's date]).

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