Is ELN p.Pro623= (c.1869C>T) pathogenic?

ELN p.Pro623= (c.1869C>T) is classified Likely benign in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-24). Ultra-rare (popmax 0.0291%, eas); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Pro623= (c.1869C>T)?

ELN p.Pro623= (c.1869C>T) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Pro623= (c.1869C>T) in the general population?

ELN p.Pro623= (c.1869C>T) is ultra-rare (popmax 0.0291%, eas) (gnomAD).

ELN p.Pro623=

c.1869C>T · rs530876235 · VCV702813

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0291%, eas)

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 · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP 1.7, phastCons 0.003
Overall
CADD	6.946	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0291% East Asian · 12/41,268 alleles

Filtering AF 0.0167% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0131%

Overall 0.00226% 35/1,549,982 alleles · ultra-rare exomes 29/1,397,822 · genomes 6/152,160 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0291%	3,439
South Asian	0.0107%	9,361
Remaining individualsnot grpmax-eligible	0.00499%	20,045
European (non-Finnish)	0.000958%	104,376

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.Pro623=
Coding: c.1869C>T
MANE Select: NM_000501
dbSNP: rs530876235
Type: single nucleotide variant
Location: chr7:74063320 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 36.20
Residue 623: the 'disordered' region

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 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-pro623 (accessed [today's date]).

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