Is ELN p.Val697Met (c.2089G>A) pathogenic?

ELN p.Val697Met (c.2089G>A) is classified Uncertain significance in ELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-11). AlphaMissense: ambiguous (0.3707); Very rare (popmax 0.00439%, sas); Associated with Inborn genetic diseases.

What condition is associated with ELN p.Val697Met (c.2089G>A)?

ELN p.Val697Met (c.2089G>A) is associated with Inborn genetic diseases, supravalvular aortic stenosis (ClinVar).

How common is ELN p.Val697Met (c.2089G>A) in the general population?

ELN p.Val697Met (c.2089G>A) is very rare (popmax 0.00439%, sas) (gnomAD).

What do computational predictors say about ELN p.Val697Met (c.2089G>A)?

AlphaMissense predicts ambiguous (score 0.3707) — an in-silico prediction, not a clinical call.

ELN p.Val697Met

c.2089G>A · rs1554689580 · VCV2236166

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3707 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3707	ambiguous
REVEL	0.068	moderately benign-leaning
SaProt	LLR -11.01	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 5.3, phastCons 0.011
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	19.77	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 V759M vs ClinVar V697M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00439% South Asian · 4/91,082 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000684% 10/1,461,662 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,770
European (non-Finnish)	0.000509%	196,647

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.Val697Met
Coding: c.2089G>A
MANE Select: NM_000501
dbSNP: rs1554689580
Type: single nucleotide variant
Location: chr7:74066734 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 697: a modified residue (allysine)

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 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
ELN c.889+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-val697met (accessed [today's date]).

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