Is ELN p.Tyr316fs (c.944dup) pathogenic?

ELN p.Tyr316fs (c.944dup) is classified Pathogenic in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-26). Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Tyr316fs (c.944dup)?

ELN p.Tyr316fs (c.944dup) is associated with supravalvular aortic stenosis (ClinVar).

ELN p.Tyr316fs

c.944dup · VCV3644463

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 17 of 33
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.75	GERP -2, phastCons 1

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

Variant & gene context

Gene: ELN
Protein: p.Tyr316fs
Coding: c.944dup
MANE Select: NM_000501
Type: Duplication
Location: chr7:74051976 (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.Tyr316Ter Pathogenic ★ 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-tyr316fs (accessed [today's date]).

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