Is ELN p.Pro578= (c.1734T>C) pathogenic?

ELN p.Pro578= (c.1734T>C) is classified Likely benign in ELN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-15). Ultra-rare (popmax 0.0329%, sas); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Pro578= (c.1734T>C)?

ELN p.Pro578= (c.1734T>C) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Pro578= (c.1734T>C) in the general population?

ELN p.Pro578= (c.1734T>C) is ultra-rare (popmax 0.0329%, sas) (gnomAD).

ELN p.Pro578=

c.1734T>C · rs561258201 · VCV515815

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, sas)

Conditions

supravalvular aortic stenosis

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -3.6	GERP -2.6
Overall
CADD	6.549	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% South Asian · 30/91,092 alleles

Filtering AF 0.0237% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.00204% 33/1,614,248 alleles · ultra-rare exomes 30/1,461,886 · genomes 3/152,362 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0329%	3,036
Remaining individualsnot grpmax-eligible	0.0048%	20,837

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.Pro578=
Coding: c.1734T>C
MANE Select: NM_000501
dbSNP: rs561258201
Type: single nucleotide variant
Location: chr7:74060488 (GRCh38)

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

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-pro578 (accessed [today's date]).

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