Is ELN p.Gly514fs (c.1539del) pathogenic?

ELN p.Gly514fs (c.1539del) is classified Pathogenic/Likely pathogenic in ELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-11-24). Very rare (popmax 0.00167%, amr); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Gly514fs (c.1539del)?

ELN p.Gly514fs (c.1539del) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Gly514fs (c.1539del) in the general population?

ELN p.Gly514fs (c.1539del) is very rare (popmax 0.00167%, amr) (gnomAD).

ELN p.Gly514fs

c.1539del · rs2486283813 · VCV2008904

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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 23 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.14	GERP 1.3, phastCons 0.002
Region caveats
Repeat context	tandem	(TGGTGT)n 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 · 1/60,010 alleles

Overall 6.84e-05% 1/1,461,874 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.Gly514fs
Coding: c.1539del
MANE Select: NM_000501
dbSNP: rs2486283813
Type: Deletion
Location: chr7:74060009 (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.Gly514= Likely benign ★ same residue
ELN p.Ala718fs Likely pathogenic ★★ same condition
ELN p.Ala99fs Pathogenic ★★ same condition
ELN p.Gln253fs Pathogenic/Likely pathogenic ★★ same condition
ELN p.Gly688fs Pathogenic ★★ same condition
ELN p.Leu56fs Pathogenic/Likely pathogenic ★★ same condition
ELN p.Pro347fs Pathogenic ★★ same condition
ELN p.Pro58fs 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-gly514fs (accessed [today's date]).

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