ERAP1 p.Ser453=
c.1359T>C · rs27529 · VCV2688362
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 66.1%, nfe) — 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 1.8 | GERP -0.36, phastCons 0.74 |
| Overall | ||
| CADD | 6.547 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
66.1%
European (non-Finnish) · 777,233/1,176,032 alleles
Filtering AF
66%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 65.9%
Overall
64.4%
1,035,892/1,609,558 alleles · common
exomes 940,932/1,457,444 · genomes 94,960/152,114 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 66.1% | 2 |
| Finnishnot grpmax-eligible | 65.1% | 2 |
| Remaining individualsnot grpmax-eligible | 62.1% | 2 |
| Admixed American | 60.5% | 2 |
| African / African-American | 60.2% | 2 |
| Middle Eastern | 59% | 2 |
| South Asian | 58.6% | 2 |
| Ashkenazi Jewishnot grpmax-eligible | 55.9% | 2 |
| East Asian | 51.5% | 2 |
| Amishnot grpmax-eligible | 44.7% | 2 |
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.Ser453=
- Coding
- c.1359T>C
- MANE Select
- NM_001040458
- dbSNP
- rs27529
- Type
- single nucleotide variant
- Location
- chr5:96790605 (GRCh38)
- Gene constraint
- LOEUF 0.947 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.78 · 27 PDB
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-ser453 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown