ENG p.Leu240=
c.720G>C · rs1830583292 · VCV2566918
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
Cardiovascular phenotype
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 3.8 | GERP 0.48, phastCons 1 |
| Overall | ||
| CADD | 12.73 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,780 alleles
Overall
0.000124%
2/1,610,784 alleles · very rare
exomes 2/1,461,074 · genomes 0/149,710 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.00223% | 44,780 |
| African / African-American | 0.00135% | 74,104 |
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
- ENG
- Protein
- p.Leu240=
- Coding
- c.720G>C
- MANE Select
- NM_001114753
- dbSNP
- rs1830583292
- Type
- single nucleotide variant
- Location
- chr9:127825327 (GRCh38)
- Gene constraint
- LOEUF 0.374 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
- Structure
- AlphaFold pLDDT 80.84 · 3 PDB
- Residue 240
- a β-strand; the 'required for interaction with gdf2' region; the 'or1, c-terminal part' region
Similar variants
- ENG c.1134+1G>T Pathogenic/Likely pathogenic ★★ same condition
- ENG c.1311+2T>A Pathogenic ★★ same condition
- ENG c.1428+1G>A Pathogenic/Likely pathogenic ★★ same condition
- ENG c.1687-1G>A Pathogenic/Likely pathogenic ★★ same condition
- ENG c.219+1G>A Pathogenic ★★ same condition
- ENG c.219+2T>C Pathogenic/Likely pathogenic ★★ same condition
- ENG c.360+1G>A Pathogenic ★★ same condition
- ENG c.360+1G>C 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/eng-p-leu240 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown