Is DES p.Glu139= (c.417A>G) pathogenic?

DES p.Glu139= (c.417A>G) is classified Likely benign in DES (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-22). Very rare (popmax 8.62e-05%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with DES p.Glu139= (c.417A>G)?

DES p.Glu139= (c.417A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is DES p.Glu139= (c.417A>G) in the general population?

DES p.Glu139= (c.417A>G) is very rare (popmax 8.62e-05%, nfe) (gnomAD).

DES p.Glu139=

c.417A>G · VCV3501188

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.62e-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 6.5	GERP 0.75, phastCons 1
Overall
CADD	14.37	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.62e-05% European (non-Finnish) · 1/1,159,596 alleles

Overall 0.000191% 3/1,572,628 alleles · very rare exomes 3/1,420,322 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00332%	30,081
European (non-Finnish)grpmax	8.62e-05%	1,159,596

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Glu139=
Coding: c.417A>G
MANE Select: NM_001927
Type: single nucleotide variant
Location: chr2:219418879 (GRCh38)
Gene constraint: LOEUF 0.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.73
Residue 139: the if rod domain; the 'coil 1a' 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.Glu139Gln Uncertain significance ★★ ⚠ same residue
DES p.Glu139Lys 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-glu139 (accessed [today's date]).

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