ERN2 p.Ile70=
c.210C>T · rs56006159 · VCV2646330
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.346%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 3.7 | GERP 0.43, phastCons 1 |
| Overall | ||
| CADD | 11.91 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.346%
European (non-Finnish) · 4,085/1,180,012 alleles
Filtering AF
0.337%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.334%
Overall
0.285%
4,608/1,614,100 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.346% | 289 |
| Remaining individualsnot grpmax-eligible | 0.291% | 343 |
| Finnishnot grpmax-eligible | 0.278% | 360 |
| Admixed American | 0.163% | 612 |
| African / African-American | 0.0573% | 1,745 |
| East Asian | 0.0401% | 2,493 |
| South Asian | 0.00439% | 22,767 |
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
- ERN2
- Protein
- p.Ile70=
- Coding
- c.210C>T
- MANE Select
- NM_033266
- dbSNP
- rs56006159
- Type
- single nucleotide variant
- Location
- chr16:23710539 (GRCh38)
- Gene constraint
- LOEUF 1.209 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.91 · 2 PDB
Similar variants
- ERN2 p.Arg868Ter Uncertain significance ★★ same type
- ERN2 p.Val69Ile Benign ★★ ⚠ same type
- ERN2 p.Ala22Val Uncertain significance ★ ⚠ same type
- ERN2 p.Ala318Asp Uncertain significance ★ ⚠ same type
- ERN2 p.Ala395Val Uncertain significance ★ ⚠ same type
- ERN2 p.Ala4Thr Uncertain significance ★ ⚠ same type
- ERN2 p.Ala760Thr Uncertain significance ★ ⚠ same type
- ERN2 p.Ala80Thr 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/ern2-p-ile70 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown