Is ELN p.Ala588Val (c.1763C>T) pathogenic?

ELN p.Ala588Val (c.1763C>T) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-25). AlphaMissense: likely benign (0.2583); Very rare (popmax 6.84e-05%); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Ala588Val (c.1763C>T)?

ELN p.Ala588Val (c.1763C>T) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala588Val (c.1763C>T) in the general population?

ELN p.Ala588Val (c.1763C>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about ELN p.Ala588Val (c.1763C>T)?

AlphaMissense predicts likely benign (score 0.2583) — an in-silico prediction, not a clinical call.

ELN p.Ala588Val

c.1763C>T · VCV3654561

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.2583	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -10.80	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 4.6	GERP 6.4, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	24.2	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 A650V vs ClinVar A588V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,778 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.Ala588Val
Coding: c.1763C>T
Type: single nucleotide variant
Location: chr7:74061116 (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-ala588val (accessed [today's date]).

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