Is ELN p.Ala2Val (c.5C>T) pathogenic?

ELN p.Ala2Val (c.5C>T) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-12). AlphaMissense: ambiguous (0.5184); Very rare (popmax 0.00401%, afr); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Ala2Val (c.5C>T)?

ELN p.Ala2Val (c.5C>T) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Ala2Val (c.5C>T) in the general population?

ELN p.Ala2Val (c.5C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

What do computational predictors say about ELN p.Ala2Val (c.5C>T)?

AlphaMissense predicts ambiguous (score 0.5184) — an in-silico prediction, not a clinical call.

ELN p.Ala2Val

c.5C>T · rs782766792 · VCV2073153

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5184 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.5184	ambiguous
REVEL	0.342	indeterminate
SaProt	LLR -8.53	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 6.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,812 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000559% 9/1,610,758 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,937
Finnishnot grpmax-eligible	0.00161%	62,258
Remaining individualsnot grpmax-eligible	0.0016%	62,306
European (non-Finnish)	0.000339%	294,820

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.Ala2Val
Coding: c.5C>T
MANE Select: NM_000501
dbSNP: rs782766792
Type: single nucleotide variant
Location: chr7:74028192 (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.Ala2Glu Conflicting classifications of pathogenicity ★ same residue
ELN p.Ala2= 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

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-ala2val (accessed [today's date]).

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