ERN2 p.Pro681=
c.2043C>A · rs200960092 · VCV736799
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0933%, 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 -20 | GERP -3.7 |
| Overall | ||
| CADD | 0.007 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0933%
African / African-American · 70/75,066 alleles
Filtering AF
0.0756%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0692%
Overall
0.0049%
79/1,613,098 alleles · ultra-rare
exomes 37/1,460,736 · genomes 42/152,362 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0933% | 1,072 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,403 |
| Admixed American | 0.00334% | 29,968 |
| South Asian | 0.0011% | 90,864 |
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.Pro681=
- Coding
- c.2043C>A
- MANE Select
- NM_033266
- dbSNP
- rs200960092
- Type
- single nucleotide variant
- Location
- chr16:23694785 (GRCh38)
- Gene constraint
- LOEUF 1.209 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 70.91 · 2 PDB
- Residue 681
- the protein kinase domain
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-pro681 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown