Is DES p.Leu187= (c.559C>T) pathogenic?

DES p.Leu187= (c.559C>T) is classified Likely benign in DES (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-04-25). Very rare (popmax 0.00391%, amr); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Leu187= (c.559C>T)?

DES p.Leu187= (c.559C>T) is associated with Cardiovascular phenotype, myofibrillar myopathy 1 (ClinVar).

How common is DES p.Leu187= (c.559C>T) in the general population?

DES p.Leu187= (c.559C>T) is very rare (popmax 0.00391%, amr) (gnomAD).

DES p.Leu187=

c.559C>T · rs1314756792 · VCV1088216

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00391%, amr)

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 2.7	GERP -2.5, phastCons 1
Overall
CADD	13.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00391% Admixed American · 2/51,122 alleles

Filtering AF 0.000649% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000243%

Overall 0.000194% 3/1,543,360 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00391%	25,561
East Asian	0.00244%	40,942

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.Leu187=
Coding: c.559C>T
MANE Select: NM_001927
dbSNP: rs1314756792
Type: single nucleotide variant
Location: chr2:219419021 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 187: 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.Leu187Arg Uncertain significance ★★ ⚠ same residue
DES p.Leu187Pro 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
DES p.Ala120Pro 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-leu187 (accessed [today's date]).

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