ERAP1 p.His68=
c.204T>C · rs73148308 · VCV768021
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Common
common (popmax 6.51%, afr) — 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 | <0.2 | all four deltas below 0.2 · A>C here scores Δ0.78 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -3.7 | GERP -4.4 |
| Overall | ||
| CADD | 0.32 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.51%
African / African-American · 4,888/75,034 alleles
Filtering AF
6.36%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 6.3%
Overall
0.367%
5,928/1,614,208 alleles · common
exomes 3,108/1,461,884 · genomes 2,820/152,324 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.51% | 15 |
| Middle Eastern | 0.643% | 155 |
| Remaining individualsnot grpmax-eligible | 0.584% | 171 |
| Admixed American | 0.453% | 221 |
| Ashkenazi Jewishnot grpmax-eligible | 0.132% | 759 |
| South Asian | 0.0307% | 3,253 |
| European (non-Finnish) | 0.0251% | 3,987 |
| East Asian | 0.00223% | 44,892 |
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.His68=
- Coding
- c.204T>C
- MANE Select
- NM_001040458
- dbSNP
- rs73148308
- Type
- single nucleotide variant
- Location
- chr5:96803723 (GRCh38)
- Gene constraint
- LOEUF 0.947 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.78 · 27 PDB
- Residue 68
- a β-strand
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-his68 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown