LPL p.Ala125=
c.375G>C · rs780831995 · VCV1113320
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
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 -16 | GERP -5.5 |
| Overall | ||
| CADD | 0.035 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,080 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000342%
5/1,461,892 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,540 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,502 |
| European (non-Finnish) | 0.000169% | 590,023 |
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
- LPL
- Protein
- p.Ala125=
- Coding
- c.375G>C
- MANE Select
- NM_000237
- dbSNP
- rs780831995
- Type
- single nucleotide variant
- Location
- chr8:19951894 (GRCh38)
- Gene constraint
- LOEUF 1.075 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.36 · 5 PDB
- Residue 125
- a turn
Similar variants
- LPL p.Ala125Thr Uncertain significance ★★ ⚠ same residue
- LPL p.Ala125Val Uncertain significance ★ same residue
- LPL c.1019-2A>T Pathogenic ★★ same type
- LPL c.1019-3C>A Pathogenic/Likely pathogenic ★★ same type
- LPL c.1139+1G>A Likely pathogenic ★★ same type
- LPL c.1139+7A>G Likely pathogenic ★★ same type
- LPL c.1322+1G>C Pathogenic/Likely pathogenic ★★ same type
- LPL c.249+1G>A Pathogenic ★★ 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/lpl-p-ala125 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown