Is ELN p.Pro511Leu (c.1532C>T) pathogenic?

ELN p.Pro511Leu (c.1532C>T) is classified Uncertain significance in ELN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-12). AlphaMissense: ambiguous (0.5035); Very rare (popmax 0.00102%, nfe); Associated with supravalvular aortic stenosis.

What condition is associated with ELN p.Pro511Leu (c.1532C>T)?

ELN p.Pro511Leu (c.1532C>T) is associated with supravalvular aortic stenosis (ClinVar).

How common is ELN p.Pro511Leu (c.1532C>T) in the general population?

ELN p.Pro511Leu (c.1532C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

What do computational predictors say about ELN p.Pro511Leu (c.1532C>T)?

AlphaMissense predicts ambiguous (score 0.5035) — an in-silico prediction, not a clinical call.

ELN p.Pro511Leu

c.1532C>T · rs2486283361 · VCV2898254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5035 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

supravalvular aortic stenosis

Computational evidence

Protein change
AlphaMissense	0.5035	ambiguous
REVEL	0.115	moderately benign-leaning
SaProt	LLR -14.01	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.24	GERP -0.36, phastCons 0.001
Regional constraint	o/e 0.91	unconstrained · MANE · 41 kb · p 0.005 · regional, not allelic
Overall
CADD	16.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P540L vs ClinVar P511L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,956 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000744% 12/1,613,968 alleles · very rare exomes 12/1,461,834 · genomes 0/152,134 · joint denominator

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.Pro511Leu
Coding: c.1532C>T
MANE Select: NM_000501
dbSNP: rs2486283361
Type: single nucleotide variant
Location: chr7:74060003 (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 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-pro511leu (accessed [today's date]).

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