Is DES p.Leu143= (c.429C>T) pathogenic?

DES p.Leu143= (c.429C>T) is classified Likely benign in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-11). Very rare (popmax 8.65e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Leu143= (c.429C>T)?

DES p.Leu143= (c.429C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DES p.Leu143= (c.429C>T) in the general population?

DES p.Leu143= (c.429C>T) is very rare (popmax 8.65e-05%, nfe) (gnomAD).

DES p.Leu143=

c.429C>T · rs796275085 · VCV2624677

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.65e-05%, 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 3.9	GERP -2.1, phastCons 1
Overall
CADD	15.39	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.65e-05% European (non-Finnish) · 1/1,156,252 alleles

Overall 7.07e-05% 1/1,413,856 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.Leu143=
Coding: c.429C>T
MANE Select: NM_001927
dbSNP: rs796275085
Type: single nucleotide variant
Location: chr2:219418891 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 143: the if rod domain; the 'linker 1' 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.Leu143Arg Uncertain significance ★ ⚠ same residue
DES p.Leu143Phe Uncertain significance ★ ⚠ same residue
DES p.Leu143Pro Uncertain significance ★ ⚠ same residue
DES p.Leu143Val Uncertain significance ★ ⚠ same residue
DES p.Arg212Ter Pathogenic/Likely pathogenic ★★ same condition
DES p.Arg454Trp Pathogenic/Likely pathogenic ★★ same condition
DES p.Glu401Asp Pathogenic/Likely pathogenic ★★ same condition
DES c.1245-3T>G 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-leu143 (accessed [today's date]).

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