Is ELN p.Val429fs (c.1283dup) pathogenic?

ELN p.Val429fs (c.1283dup) is classified Pathogenic in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-13). Very rare (popmax 0.00167%, amr); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Val429fs (c.1283dup)?

ELN p.Val429fs (c.1283dup) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Val429fs (c.1283dup) in the general population?

ELN p.Val429fs (c.1283dup) is very rare (popmax 0.00167%, amr) (gnomAD).

ELN p.Val429fs

c.1283dup · VCV3728914

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 20 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -11	GERP -9.8
Region caveats
Repeat context	tandem	GGAGTCGGAGGTGTCCCT simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,958 alleles

Overall 6.84e-05% 1/1,461,452 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: ELN
Protein: p.Val429fs
Coding: c.1283dup
MANE Select: NM_000501
Type: Duplication
Location: chr7:74056401 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20

Full ELN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

supravalvular aortic stenosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ELN p.Val429= Likely benign ★★ same residue
ELN p.Ala288fs Pathogenic ★★ same condition
ELN p.Val282fs Pathogenic ★★ same condition
ELN p.Gly345_Pro352dup Uncertain significance ★★ same condition
ELN c.1414+11dup Likely benign ★★ same condition
ELN p.646GLG[3] Likely benign ★★ same condition
ELN p.Ala362fs Pathogenic ★ same condition
ELN p.Ala372fs 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/eln-p-val429fs (accessed [today's date]).

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