Is ELN p.Gly607Arg (c.1819G>A) pathogenic?

ELN p.Gly607Arg (c.1819G>A) is classified Uncertain significance in ELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-25). AlphaMissense: likely pathogenic (0.6567); Ultra-rare (popmax 0.0101%, amr); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Gly607Arg (c.1819G>A)?

ELN p.Gly607Arg (c.1819G>A) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Gly607Arg (c.1819G>A) in the general population?

ELN p.Gly607Arg (c.1819G>A) is ultra-rare (popmax 0.0101%, amr) (gnomAD).

What do computational predictors say about ELN p.Gly607Arg (c.1819G>A)?

AlphaMissense predicts likely pathogenic (score 0.6567) — an in-silico prediction, not a clinical call.

ELN p.Gly607Arg

c.1819G>A · rs781963804 · VCV1691674

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6567 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.6567	likely pathogenic
REVEL	0.278	benign-leaning
SaProt	LLR -12.39	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 5.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	22.7	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 G669R vs ClinVar G607R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0101% Admixed American · 6/59,318 alleles

Filtering AF 0.00432% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00298%

Overall 0.00224% 36/1,609,494 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0101%	9,886
Remaining individualsnot grpmax-eligible	0.00481%	20,771
East Asian	0.00223%	44,780
European (non-Finnish)	0.00212%	47,156
South Asian	0.00112%	89,340

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.Gly607Arg
Coding: c.1819G>A
MANE Select: NM_000501
dbSNP: rs781963804
Type: single nucleotide variant
Location: chr7:74063185 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 607: a modified residue (4-hydroxyproline; partial)

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.Gly607= Benign/Likely benign ★★ same residue
ELN p.Gly607Ala 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-gly607arg (accessed [today's date]).

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