LONP1 p.Pro22=
c.66G>T · rs753490076 · VCV1605112
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00821%, amr)
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 -1.4 | GERP -2.8 |
| Overall | ||
| CADD | 5.081 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00821%
Admixed American · 4/48,704 alleles
Filtering AF
0.00271%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00169%
Overall
0.000654%
10/1,529,406 alleles · very rare
exomes 7/1,377,264 · genomes 3/152,142 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.00821% | 12,176 |
| East Asian | 0.00253% | 39,524 |
| Remaining individualsnot grpmax-eligible | 0.00169% | 59,262 |
| European (non-Finnish) | 0.00035% | 285,859 |
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
- LONP1
- Protein
- p.Pro22=
- Coding
- c.66G>T
- MANE Select
- NM_004793
- dbSNP
- rs753490076
- Type
- single nucleotide variant
- Location
- chr19:5720067 (GRCh38)
- Gene constraint
- LOEUF 0.448 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.35 · 36 PDB
Similar variants
- LONP1 p.Pro22Arg Uncertain significance ★ ⚠ same residue
- LONP1 p.Pro22_Arg30del Uncertain significance ★★ same residue
- LONP1 p.Arg301Trp Likely pathogenic ★★ same type
- LONP1 p.Ala26Pro Uncertain significance ★★ ⚠ same type
- LONP1 p.Ala27Pro Uncertain significance ★★ ⚠ same type
- LONP1 p.Ala27Ser Uncertain significance ★★ ⚠ same type
- LONP1 p.Ala337Thr Uncertain significance ★★ ⚠ same type
- LONP1 p.Ala901Val 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/lonp1-p-pro22 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown