LIPA p.Arg396=
c.1188G>A · rs750001661 · VCV558136
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
very rare (popmax 0.000605%, nfe)
Conditions
3
Cardiovascular phenotype
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 1.3 | GERP 0.88, phastCons 0.75 |
| Overall | ||
| CADD | 8.202 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000605%
European (non-Finnish) · 7/1,157,342 alleles
Filtering AF
0.000252%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000162%
Overall
0.000441%
7/1,588,730 alleles · very rare
exomes 6/1,436,582 · genomes 1/152,148 · joint denominator
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
- LIPA
- Protein
- p.Arg396=
- Coding
- c.1188G>A
- MANE Select
- NM_000235
- dbSNP
- rs750001661
- Type
- single nucleotide variant
- Location
- chr10:89214840 (GRCh38)
- Structure
- AlphaFold pLDDT 89.74
Similar variants
- LIPA c.111+1G>A Pathogenic/Likely pathogenic ★★ same condition
- LIPA c.539-2A>G Pathogenic ★★ same condition
- LIPA c.675+2T>G Likely pathogenic ★★ same condition
- LIPA c.676-2A>T Pathogenic ★★ same condition
- LIPA c.822+1G>A Likely pathogenic ★★ same condition
- LIPA c.823-2A>G Likely pathogenic ★★ same condition
- LIPA c.894+1G>A Pathogenic ★★ same condition
- LIPA p.Ala307Asp Likely pathogenic ★★ same condition
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/lipa-p-arg396 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown