Is ELN p.Gly272Arg (c.814G>A) pathogenic?

ELN p.Gly272Arg (c.814G>A) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.8447); Ultra-rare (popmax 0.0121%, sas); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Gly272Arg (c.814G>A)?

ELN p.Gly272Arg (c.814G>A) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Gly272Arg (c.814G>A) in the general population?

ELN p.Gly272Arg (c.814G>A) is ultra-rare (popmax 0.0121%, sas) (gnomAD).

What do computational predictors say about ELN p.Gly272Arg (c.814G>A)?

AlphaMissense predicts likely pathogenic (score 0.8447) — an in-silico prediction, not a clinical call.

ELN p.Gly272Arg

c.814G>A · rs527441189 · VCV2778493

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8447 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.8447	likely pathogenic
REVEL	0.33	indeterminate
SaProt	LLR -12.58	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 5.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0121% South Asian · 11/91,086 alleles

Filtering AF 0.00676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00522%

Overall 0.000929% 15/1,614,208 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0121%	8,281
European (non-Finnish)	0.000339%	295,009

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.Gly272Arg
Coding: c.814G>A
MANE Select: NM_000501
dbSNP: rs527441189
Type: single nucleotide variant
Location: chr7:74051764 (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.Gly272Ter Pathogenic ★ 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-gly272arg (accessed [today's date]).

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