ERAP1 p.His417=
c.1251C>T · rs3213809 · VCV2688437
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 21.7%, amr) — too common for a highly-penetrant pathogenic allele
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 0.04 | GERP 0.47, phastCons 0.36 |
| Overall | ||
| CADD | 6.601 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
21.7%
Admixed American · 13,036/60,008 alleles
Filtering AF
21.4%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 21.3%
Overall
12.9%
207,680/1,613,472 alleles · common
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 21.7% | 5 |
| Amishnot grpmax-eligible | 17.3% | 6 |
| Finnishnot grpmax-eligible | 14.2% | 7 |
| European (non-Finnish) | 13.4% | 7 |
| Ashkenazi Jewishnot grpmax-eligible | 13% | 8 |
| Remaining individualsnot grpmax-eligible | 12.7% | 8 |
| Middle Eastern | 12.5% | 8 |
| South Asian | 12% | 8 |
| East Asian | 3.02% | 33 |
| African / African-American | 3.01% | 33 |
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
- ERAP1
- Protein
- p.His417=
- Coding
- c.1251C>T
- MANE Select
- NM_001040458
- dbSNP
- rs3213809
- Type
- single nucleotide variant
- Location
- chr5:96792130 (GRCh38)
- Gene constraint
- LOEUF 0.947 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.78 · 27 PDB
- Residue 417
- a disulfide bond
Similar variants
- ERAP1 p.Ala356= Benign ★★ same type
- ERAP1 p.Gly514Arg Benign/Likely benign ★★ same type
- ERAP1 p.Ile915Thr Likely benign ★★ ⚠ same type
- ERAP1 p.Ser18= Benign/Likely benign ★★ same type
- ERAP1 p.Tyr57= Benign/Likely benign ★★ same type
- ERAP1 p.Tyr789= Benign ★★ same type
- ERAP2 p.Leu411Arg Benign/Likely benign ★★ ⚠ same type
- CAST p.Leu618Phe 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/erap1-p-his417 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown