Is DES p.Arg386= (c.1158C>T) pathogenic?

DES p.Arg386= (c.1158C>T) is classified Conflicting classifications of pathogenicity in DES (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-10-01). Very rare (popmax 0.00659%, sas); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Arg386= (c.1158C>T)?

DES p.Arg386= (c.1158C>T) is associated with Cardiovascular phenotype, cardiomyopathy, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Arg386= (c.1158C>T) in the general population?

DES p.Arg386= (c.1158C>T) is very rare (popmax 0.00659%, sas) (gnomAD).

DES p.Arg386=

c.1158C>T · rs774323736 · VCV285963

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.40	donor gain · deltas
Constraint at this position
Conservation	phyloP -1.5	GERP -3.7
Overall
CADD	17.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00659% South Asian · 6/91,074 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00248% 40/1,614,082 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,179
East Asian	0.00446%	22,432
European (non-Finnish)	0.00254%	39,334
Admixed American	0.00167%	60,020
Remaining individualsnot grpmax-eligible	0.0016%	62,504

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.Arg386=
Coding: c.1158C>T
MANE Select: NM_001927
dbSNP: rs774323736
Type: single nucleotide variant
Location: chr2:219421474 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 386: 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: cardiomyopathy myofibrillar myopathy 1

Similar variants

DES p.Arg386Cys Uncertain significance ★★ ⚠ same residue
DES p.Arg386His Uncertain significance ★★ ⚠ same residue
DES p.Arg386Leu 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
DES c.735+3A>G 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-arg386 (accessed [today's date]).

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