MPO p.Leu250=
c.750C>G · VCV4936172
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.169%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.77 | GERP -0.92, phastCons 0.16 |
| Overall | ||
| CADD | 8.517 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.169%
African / African-American · 127/75,052 alleles
Filtering AF
0.145%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.136%
Overall
0.00862%
139/1,612,902 alleles · rare
exomes 66/1,460,536 · genomes 73/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.169% | 591 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,490 |
| Admixed American | 0.00501% | 19,951 |
| European (non-Finnish) | 0.000339% | 294,875 |
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
- MPO
- Protein
- p.Leu250=
- Coding
- c.750C>G
- MANE Select
- NM_000250
- Type
- single nucleotide variant
- Location
- chr17:58279143 (GRCh38)
- Gene constraint
- LOEUF 0.992 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 89.55 · 49 PDB
- Residue 250
- an α-helix
Similar variants
- MPO p.Gln241Ter Pathogenic/Likely pathogenic ★★ same type
- MPO p.Trp602Ter Likely pathogenic ★★ same type
- MPO p.Arg691Gln Uncertain significance ★★ ⚠ same type
- MPO p.Met356Val Uncertain significance ★★ ⚠ same type
- MPO c.2031-6A>C Benign ★★ same type
- MPO p.Arg604Cys Likely benign ★★ ⚠ same type
- MPO p.Asn729= Benign/Likely benign ★★ same type
- MPO p.Pro105= Likely benign ★★ 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/mpo-p-leu250 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown