Is ELN p.Val298Ile (c.892G>A) pathogenic?

ELN p.Val298Ile (c.892G>A) is classified Benign/Likely benign in ELN (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). AlphaMissense: likely benign (0.1505); Low-frequency (popmax 1.13%, afr); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Val298Ile (c.892G>A)?

ELN p.Val298Ile (c.892G>A) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Val298Ile (c.892G>A) in the general population?

ELN p.Val298Ile (c.892G>A) is low-frequency (popmax 1.13%, afr) (gnomAD).

What do computational predictors say about ELN p.Val298Ile (c.892G>A)?

AlphaMissense predicts likely benign (score 0.1505) — an in-silico prediction, not a clinical call.

ELN p.Val298Ile

c.892G>A · rs41526244 · VCV238950

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.1505 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.13%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.1505	likely benign
REVEL	0.063	moderately benign-leaning
SaProt	LLR -9.51	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 7.2	GERP 4.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	16.96	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 1.13% African / African-American · 845/75,052 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.04%

Overall 0.0672% 1,084/1,613,972 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.13%	89
Admixed American	0.122%	822
Remaining individualsnot grpmax-eligible	0.109%	919
Middle Eastern	0.0331%	3,019
European (non-Finnish)	0.00771%	12,967
South Asian	0.00439%	22,772
East Asian	0.00223%	44,860

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.Val298Ile
Coding: c.892G>A
MANE Select: NM_000501
dbSNP: rs41526244
Type: single nucleotide variant
Location: chr7:74051926 (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.Val298= Likely benign ★ same residue
ELN p.Val298Ala Uncertain significance ★ ⚠ 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-val298ile (accessed [today's date]).

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