LPP p.Ala365=
c.1095G>A · rs139912286 · VCV756191
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0562%, 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 -2.4 | GERP -5.7 |
| Overall | ||
| CADD | 1.464 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0562%
African / African-American · 42/74,774 alleles
Filtering AF
0.0426%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.038%
Overall
0.0181%
291/1,610,980 alleles · ultra-rare
exomes 252/1,458,858 · genomes 39/152,122 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0562% | 1,780 |
| Middle Eastern | 0.0496% | 2,018 |
| South Asian | 0.0297% | 3,363 |
| Remaining individualsnot grpmax-eligible | 0.0257% | 3,894 |
| European (non-Finnish) | 0.0163% | 6,140 |
| East Asian | 0.0111% | 8,974 |
| Admixed American | 0.0067% | 14,935 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00342% | 29,262 |
| Finnishnot grpmax-eligible | 0.00158% | 63,398 |
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.Ala365=
- Coding
- c.1095G>A
- MANE Select
- NM_001375462
- dbSNP
- rs139912286
- Type
- single nucleotide variant
- Location
- chr3:188609826 (GRCh38)
- Gene constraint
- LOEUF 0.765 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 60.99
- Residue 365
- the 'disordered' region
Similar variants
- LPP p.Arg140Trp Uncertain significance ★★ ⚠ same type
- LPP c.1113+51T>C Benign ★★ same type
- LPP c.1240+249G>A Benign ★★ same type
- LPP c.1240+75A>G Benign ★★ same type
- LPP c.1410+155C>T Benign ★★ same type
- LPP c.1410+157T>C Benign ★★ same type
- LPP c.1410+162G>A Benign ★★ same type
- LPP c.1410+165T>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-ala365 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown