ERN1 p.Leu786=
c.2358C>T · rs61736508 · VCV711661
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.34%, afr)
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 0.43 | GERP 0.17, phastCons 0.99 |
| Overall | ||
| CADD | 6.187 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.34%
African / African-American · 1,754/74,938 alleles
Filtering AF
2.25%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.21%
Overall
0.122%
1,958/1,608,042 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.34% | 43 |
| Remaining individualsnot grpmax-eligible | 0.132% | 758 |
| Admixed American | 0.124% | 809 |
| Middle Eastern | 0.0668% | 1,498 |
| South Asian | 0.00661% | 15,135 |
| European (non-Finnish) | 0.00323% | 30,927 |
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
- ERN1
- Protein
- p.Leu786=
- Coding
- c.2358C>T
- MANE Select
- NM_001433
- dbSNP
- rs61736508
- Type
- single nucleotide variant
- Location
- chr17:64049098 (GRCh38)
- Gene constraint
- LOEUF 0.498 · pLI 0.95 (gnomAD)
- Structure
- AlphaFold pLDDT 73.50 · 26 PDB
- Residue 786
- an α-helix; the protein kinase domain
Similar variants
- ERN1 p.Pro550Arg Benign ★★ same type
- ERN1 p.Ala427Thr Uncertain significance ★ ⚠ same type
- ERN1 p.Ala431Pro Uncertain significance ★ ⚠ same type
- ERN1 p.Ala435Asp Uncertain significance ★ ⚠ same type
- ERN1 p.Ala435Thr Uncertain significance ★ ⚠ same type
- ERN1 p.Ala435Val Uncertain significance ★ ⚠ same type
- ERN1 p.Ala641Gly Uncertain significance ★ ⚠ same type
- ERN1 p.Ala641Val Uncertain significance ★ ⚠ same type
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/ern1-p-leu786 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown