Is ELN p.Ala363Val (c.1088C>T) pathogenic?

ELN p.Ala363Val (c.1088C>T) is classified Uncertain significance in ELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-29). AlphaMissense: likely benign (0.1577); Ultra-rare (popmax 0.0224%, eas); Associated with Inborn genetic diseases.

What condition is associated with ELN p.Ala363Val (c.1088C>T)?

ELN p.Ala363Val (c.1088C>T) is associated with Inborn genetic diseases, supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala363Val (c.1088C>T) in the general population?

ELN p.Ala363Val (c.1088C>T) is ultra-rare (popmax 0.0224%, eas) (gnomAD).

What do computational predictors say about ELN p.Ala363Val (c.1088C>T)?

AlphaMissense predicts likely benign (score 0.1577) — an in-silico prediction, not a clinical call.

ELN p.Ala363Val

c.1088C>T · rs571843793 · VCV2186940

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1577 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0224%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1577	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -5.95	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -6.5, phastCons 0.002
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	16.58	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0224% East Asian · 10/44,736 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00919%

Overall 0.00373% 60/1,610,356 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0224%	4,474
Remaining individualsnot grpmax-eligible	0.00802%	12,476
European (non-Finnish)	0.00356%	28,076
African / African-American	0.00271%	36,943
South Asian	0.0011%	90,804

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.Ala363Val
Coding: c.1088C>T
MANE Select: NM_000501
dbSNP: rs571843793
Type: single nucleotide variant
Location: chr7:74053301 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: supravalvular aortic stenosis

Similar variants

ELN p.Ala363= Likely benign ★ same residue
ELN c.377-2A>G Pathogenic/Likely pathogenic ★★ same condition
ELN c.643+1G>C Likely pathogenic ★★ same condition
ELN c.686-2A>G Likely pathogenic ★★ same condition
ELN c.800-1G>A Pathogenic/Likely pathogenic ★★ same condition
ELN c.800-2A>G Pathogenic ★★ same condition
ELN c.800-3C>G Pathogenic ★★ same condition
ELN c.82+1G>A Pathogenic/Likely 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-ala363val (accessed [today's date]).

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