Is DES p.Ser82= (c.246C>T) pathogenic?

DES p.Ser82= (c.246C>T) is classified Likely benign in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-20). Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with DES p.Ser82= (c.246C>T)?

DES p.Ser82= (c.246C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is DES p.Ser82= (c.246C>T) in the general population?

DES p.Ser82= (c.246C>T) is absent from gnomAD v4.1 (gnomAD).

DES p.Ser82=

c.246C>T · rs2545246816 · VCV2450705

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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
Pangolin	Δ0.24	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.014	GERP -2.7, phastCons 0.87
Overall
CADD	11.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DES
Protein: p.Ser82=
Coding: c.246C>T
MANE Select: NM_001927
dbSNP: rs2545246816
Type: single nucleotide variant
Location: chr2:219418708 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 82: the 'head' 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.Ser82Phe Uncertain significance ★★ ⚠ same residue
DES p.Ser82Pro 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
DES c.639+4A>G Uncertain significance ★★ same condition
DES p.Ala135Gly 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-ser82 (accessed [today's date]).

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