Is ELN p.Leu540Val (c.1618C>G) pathogenic?

ELN p.Leu540Val (c.1618C>G) is classified Pathogenic in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-30). AlphaMissense: likely benign (0.1553); Absent from gnomAD v4.1; Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Leu540Val (c.1618C>G)?

ELN p.Leu540Val (c.1618C>G) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Leu540Val (c.1618C>G) in the general population?

ELN p.Leu540Val (c.1618C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ELN p.Leu540Val (c.1618C>G)?

AlphaMissense predicts likely benign (score 0.1553) — an in-silico prediction, not a clinical call.

ELN p.Leu540Val

c.1618C>G · VCV3661346

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1553 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.1553	likely benign ⚠ discordant with ClinVar
REVEL	0.013	strongly benign-leaning
SaProt	LLR -7.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.75	gain · loss 0.73 · independent
Constraint at this position
Conservation	phyloP -0.29	GERP 2.5, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L569V vs ClinVar L540V) — verify the residue.

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: ELN
Protein: p.Leu540Val
Coding: c.1618C>G
Type: single nucleotide variant
Location: chr7:74060181 (GRCh38)

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

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-leu540val (accessed [today's date]).

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