LONP1 p.Ser855=
c.2565C>T · rs146948426 · VCV714754
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.97%, afr)
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 -7.9 | GERP -2.8 |
| Overall | ||
| CADD | 0.057 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.97%
African / African-American · 1,481/75,034 alleles
Filtering AF
1.89%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.86%
Overall
0.108%
1,740/1,611,790 alleles · low-frequency
exomes 901/1,459,460 · genomes 839/152,330 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.97% | 51 |
| Remaining individualsnot grpmax-eligible | 0.157% | 637 |
| Middle Eastern | 0.149% | 673 |
| Admixed American | 0.135% | 740 |
| South Asian | 0.00769% | 13,006 |
| European (non-Finnish) | 0.00543% | 18,418 |
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.Ser855=
- Coding
- c.2565C>T
- MANE Select
- NM_004793
- dbSNP
- rs146948426
- Type
- single nucleotide variant
- Location
- chr19:5693436 (GRCh38)
- Gene constraint
- LOEUF 0.448 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 77.35 · 36 PDB
- Residue 855
- an α-helix; the lon proteolytic domain; an active site
Similar variants
- 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
- LONP1 p.Arg15Pro Uncertain significance ★★ ⚠ same type
- LONP1 p.Arg301Gln 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-ser855 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown