Is ELN p.Gly384Arg (c.1150G>A) pathogenic?

ELN p.Gly384Arg (c.1150G>A) is classified Uncertain significance in ELN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-08-06). AlphaMissense: likely pathogenic (0.905); Ultra-rare (popmax 0.0167%, mid); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Gly384Arg (c.1150G>A)?

ELN p.Gly384Arg (c.1150G>A) is associated with supravalvular aortic stenosis, cutis laxa, autosomal dominant 1, Williams syndrome (ClinVar).

How common is ELN p.Gly384Arg (c.1150G>A) in the general population?

ELN p.Gly384Arg (c.1150G>A) is ultra-rare (popmax 0.0167%, mid) (gnomAD).

What do computational predictors say about ELN p.Gly384Arg (c.1150G>A)?

AlphaMissense predicts likely pathogenic (score 0.905) — an in-silico prediction, not a clinical call.

ELN p.Gly384Arg

c.1150G>A · rs782359367 · VCV1437068

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely pathogenic

0.905 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0167%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.905	likely pathogenic · top 8% in ELN
REVEL	0.223	benign-leaning
SaProt	LLR -12.66	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.40	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 6.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	34.0	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 0.0167% Middle Eastern · 1/5,988 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.0031% 50/1,613,960 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0167%	5,988
Remaining individualsnot grpmax-eligible	0.0048%	20,825
South Asian	0.00439%	22,767
European (non-Finnish)	0.00339%	29,501
Finnishnot grpmax-eligible	0.00156%	64,028
African / African-American	0.00133%	74,938

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.Gly384Arg
Coding: c.1150G>A
MANE Select: NM_000501
dbSNP: rs782359367
Type: single nucleotide variant
Location: chr7:74054769 (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

Also linked: cutis laxa, autosomal dominant 1 Williams syndrome

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-gly384arg (accessed [today's date]).

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