ELN p.Pro180=
c.540A>C · rs145778002 · VCV1023961
Uncertain significance
Multiple submitters
Classification
Uncertain significance
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00263%, nfe)
Conditions
1
supravalvular aortic stenosis
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.35 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.50 | loss · gain 0.01 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 7.9 | GERP 5, phastCons 1 |
| Overall | ||
| CADD | 18.04 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00263%
European (non-Finnish) · 31/1,180,036 alleles
Filtering AF
0.00188%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00164%
Overall
0.00204%
33/1,613,928 alleles · very rare
exomes 28/1,461,688 · genomes 5/152,240 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00263% | 38,066 |
| Admixed American | 0.00167% | 60,012 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,486 |
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.Pro180=
- Coding
- c.540A>C
- MANE Select
- NM_000501
- dbSNP
- rs145778002
- Type
- single nucleotide variant
- Location
- chr7:74045292 (GRCh38)
- Gene constraint
- LOEUF 0.696 · pLI <0.01 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 36.20
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-pro180 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown