ERAP1 p.Cys743=
c.2229C>T · rs146423238 · VCV720301
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 2.28%, sas)
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 · G>T here scores Δ0.75 · evaluated, not missing |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -1.9 | GERP -4.4 |
| Overall | ||
| CADD | 0.457 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.28%
South Asian · 2,080/91,084 alleles
Filtering AF
2.2%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.17%
Overall
0.567%
9,152/1,614,120 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 2.28% | 44 |
| Ashkenazi Jewishnot grpmax-eligible | 1.75% | 57 |
| Middle Eastern | 0.907% | 110 |
| European (non-Finnish) | 0.503% | 199 |
| Remaining individualsnot grpmax-eligible | 0.49% | 204 |
| Admixed American | 0.243% | 411 |
| Finnishnot grpmax-eligible | 0.0812% | 1,231 |
| African / African-American | 0.0733% | 1,364 |
| East Asian | 0.0178% | 5,610 |
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.Cys743=
- Coding
- c.2229C>T
- MANE Select
- NM_001040458
- dbSNP
- rs146423238
- Type
- single nucleotide variant
- Location
- chr5:96783107 (GRCh38)
- Gene constraint
- LOEUF 0.947 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.78 · 27 PDB
- Residue 743
- an α-helix; 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-cys743 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown