LRPAP1 p.Ala109=
c.327G>A · rs142669297 · VCV732263
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.19%, 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 -9.8 | GERP -2.7 |
| Overall | ||
| CADD | 0.159 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.19%
African / African-American · 892/75,052 alleles
Filtering AF
1.12%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.1%
Overall
0.067%
1,082/1,614,188 alleles · low-frequency
exomes 547/1,461,860 · genomes 535/152,328 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 1.19% | 84 |
| Admixed American | 0.117% | 858 |
| Middle Eastern | 0.099% | 1,010 |
| Remaining individualsnot grpmax-eligible | 0.0976% | 1,025 |
| European (non-Finnish) | 0.00432% | 23,138 |
| South Asian | 0.0022% | 45,540 |
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
- LRPAP1
- Protein
- p.Ala109=
- Coding
- c.327G>A
- MANE Select
- NM_002337
- dbSNP
- rs142669297
- Type
- single nucleotide variant
- Location
- chr4:3524929 (GRCh38)
- Gene constraint
- LOEUF 1.375 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 75.80 · 10 PDB
- Residue 109
- an α-helix
Similar variants
- LRPAP1 p.Arg110Thr Uncertain significance ★★ ⚠ same type
- LRPAP1 p.Asp211Asn Likely benign ★★ same type
- LRPAP1 p.Gly166= Benign ★★ same type
- LRPAP1 p.Gly166Ser Benign/Likely benign ★★ same type
- LRPAP1 p.Ile199Val Benign ★★ same type
- LRPAP1 c.751+1G>A Likely pathogenic ★ same type
- LRPAP1 c.593-98C>T Uncertain significance ★ same type
- LRPAP1 p.Ala264Ser 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/lrpap1-p-ala109 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown