Is ELN p.Thr5= (c.15G>A) pathogenic?

ELN p.Thr5= (c.15G>A) is classified Likely benign in ELN (ClinVar, Single submitter, 2 submitters; last evaluated 2024-09-06). Ultra-rare (popmax 0.0176%, sas); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Thr5= (c.15G>A)?

ELN p.Thr5= (c.15G>A) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Thr5= (c.15G>A) in the general population?

ELN p.Thr5= (c.15G>A) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

ELN p.Thr5=

c.15G>A · rs782452483 · VCV2714512

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

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 0.89	GERP -7, phastCons 0.99
Overall
CADD	7.096	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% South Asian · 16/90,908 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.009%

Overall 0.00161% 26/1,610,932 alleles · ultra-rare exomes 25/1,459,440 · genomes 1/151,492 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,682
Remaining individualsnot grpmax-eligible	0.00482%	20,766
Admixed American	0.00334%	29,945
European (non-Finnish)	0.000424%	235,909

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.Thr5=
Coding: c.15G>A
MANE Select: NM_000501
dbSNP: rs782452483
Type: single nucleotide variant
Location: chr7:74028202 (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.Thr5Arg Uncertain significance ★ ⚠ same residue
ELN p.Thr5Met 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

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-thr5 (accessed [today's date]).

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