Is ELN p.Gly422Ser (c.1263_1264inv) pathogenic?

ELN p.Gly422Ser (c.12631264inv) is classified Likely benign in ELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-02). Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Gly422Ser (c.1263_1264inv)?

ELN p.Gly422Ser (c.1263_1264inv) is associated with supravalvular aortic stenosis (ClinVar).

ELN p.Gly422Ser

c.1263_1264inv · VCV422996

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.9	GERP -0.83
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Region caveats
Repeat context	tandem	GGAGTCGGAGGTGTCCCT simple repeat · ambiguous alignment · confidence, not pathogenicity

Variant & gene context

Gene: ELN
Protein: p.Gly422Ser
Coding: c.1263_1264inv
MANE Select: NM_000501
Type: Inversion
Location: chr7:74056383 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 422: a UniProt-annotated variant site (in)

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.Gly422Arg 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
ELN c.82+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-gly422ser (accessed [today's date]).

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