Is DES p.Arg350Gln (c.1049G>A) pathogenic?

DES p.Arg350Gln (c.1049G>A) is classified Uncertain significance in DES (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-12-31). AlphaMissense: likely benign (0.1109); Very rare (popmax 0.00517%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Arg350Gln (c.1049G>A)?

DES p.Arg350Gln (c.1049G>A) is associated with Cardiovascular phenotype, neurogenic scapuloperoneal syndrome, Kaeser type, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Arg350Gln (c.1049G>A) in the general population?

DES p.Arg350Gln (c.1049G>A) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about DES p.Arg350Gln (c.1049G>A)?

AlphaMissense predicts likely benign (score 0.1109) — an in-silico prediction, not a clinical call.

DES p.Arg350Gln

c.1049G>A · rs57965306 · VCV596421

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1109 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1109	likely benign
REVEL	0.813	moderately pathogenic-leaning
SaProt	LLR -8.24	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 7,524 bp · p 0.05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00517% European (non-Finnish) · 61/1,180,030 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.00403% 65/1,613,984 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
South Asian	0.00329%	30,360
East Asian	0.00223%	44,884

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.Arg350Gln
Coding: c.1049G>A
MANE Select: NM_001927
dbSNP: rs57965306
Type: single nucleotide variant
Location: chr2:219421365 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 350: the 'coil 2b' region; the if rod domain; a UniProt-annotated variant site (in kaeser syndrome and mfm1; incapable of de novo formation of a desmin intermediate filaments network; exerts a dominant negative effect on the ordered lateral arrangement of desmin subunits; may produce structural changes; forms subsarcolemmal aggregates); 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.Arg350Pro Pathogenic ★★ same residue
DES p.Arg350= Conflicting classifications of pathogenicity ★ same residue
DES p.Arg350Leu Uncertain significance ★ ⚠ same residue
DES p.Arg350Trp Conflicting classifications of pathogenicity ★ ⚠ 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-arg350gln (accessed [today's date]).

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