ERN2 p.Phe472=
c.1416T>C · rs74012349 · VCV736800
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.614%, afr)
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 · A>T here scores Δ0.23 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.72 | GERP -0.59, phastCons 0.021 |
| Overall | ||
| CADD | 1.66 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.614%
African / African-American · 461/75,050 alleles
Filtering AF
0.568%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.55%
Overall
0.0328%
530/1,614,124 alleles · rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.614% | 163 |
| Remaining individualsnot grpmax-eligible | 0.0656% | 1,525 |
| Admixed American | 0.04% | 2,501 |
| South Asian | 0.0011% | 91,082 |
| European (non-Finnish) | 0.000254% | 393,335 |
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.Phe472=
- Coding
- c.1416T>C
- MANE Select
- NM_033266
- dbSNP
- rs74012349
- Type
- single nucleotide variant
- Location
- chr16:23700648 (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-phe472 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown