LPP p.Ser145=
c.435C>T · VCV3352448
Likely benign
No assertion criteria
Classification
Likely benign
ClinVar
Review
No assertion criteria ☆☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.204%, afr)
Conditions
1
LPP-related disorder
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 -0.052 | GERP -2.5 |
| Overall | ||
| CADD | 1.636 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.204%
African / African-American · 152/74,372 alleles
Filtering AF
0.178%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.168%
Overall
0.0111%
178/1,599,986 alleles · rare
exomes 74/1,448,122 · genomes 104/151,864 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.204% | 489 |
| Admixed American | 0.0326% | 3,064 |
| Remaining individualsnot grpmax-eligible | 0.00971% | 10,302 |
| European (non-Finnish) | 8.54e-05% | 1,171,547 |
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
- LPP
- Protein
- p.Ser145=
- Coding
- c.435C>T
- MANE Select
- NM_001375462
- Type
- single nucleotide variant
- Location
- chr3:188609166 (GRCh38)
- Gene constraint
- LOEUF 0.765 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99
- Residue 145
- the 'disordered' region
Disease context
LPP-related disorder
Similar variants
- LPP c.1589+8A>G Likely benign same condition
- LPP p.Ala302= Likely benign same condition
- LPP p.Arg22Trp Likely benign ⚠ same condition
- LPP p.Gly245= Likely benign same condition
- LPP p.Pro363Ser Benign same condition
- LPP p.Thr212Met Likely benign ⚠ same condition
- LPP p.Arg140Trp Uncertain significance ★★ ⚠ same type
- LPP c.1113+51T>C 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/lpp-p-ser145 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown