Is ELN p.Phe703= (c.2109C>T) pathogenic?

ELN p.Phe703= (c.2109C>T) is classified Benign/Likely benign in ELN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-21). Ultra-rare (popmax 0.0509%, nfe); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Phe703= (c.2109C>T)?

ELN p.Phe703= (c.2109C>T) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Phe703= (c.2109C>T) in the general population?

ELN p.Phe703= (c.2109C>T) is ultra-rare (popmax 0.0509%, nfe) (gnomAD).

ELN p.Phe703=

c.2109C>T · rs149755814 · VCV360662

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0509%, nfe)

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3	GERP -6.5
Overall
CADD	4.659	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0509% European (non-Finnish) · 600/1,179,684 alleles

Filtering AF 0.0475% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0461%

Overall 0.0409% 660/1,613,612 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0509%	1,966
Remaining individualsnot grpmax-eligible	0.0496%	2,016
Admixed American	0.0217%	4,615
African / African-American	0.0147%	6,818
Finnishnot grpmax-eligible	0.00313%	31,979
East Asian	0.00223%	44,850
South Asian	0.0022%	45,536

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.Phe703=
Coding: c.2109C>T
MANE Select: NM_000501
dbSNP: rs149755814
Type: single nucleotide variant
Location: chr7:74066754 (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.Phe703Leu 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-phe703 (accessed [today's date]).

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