Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 7 submitters
gnomAD v4.1
Common
common (popmax 35.9%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
1
neutral lipid storage myopathy
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 0.44, phastCons 0.049 |
| Overall | ||
| CADD | 7.675 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
35.9%
African / African-American · 26,183/72,992 alleles
Filtering AF
35.5%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 35.4%
Overall
18%
276,654/1,534,204 alleles · common
exomes 243,905/1,381,988 · genomes 32,749/152,216 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 35.9% | 3 |
| East Asian | 31.2% | 3 |
| South Asian | 25.3% | 4 |
| Remaining individualsnot grpmax-eligible | 18.5% | 5 |
| European (non-Finnish) | 16.6% | 6 |
| Ashkenazi Jewishnot grpmax-eligible | 12.5% | 8 |
| Admixed American | 11.8% | 8 |
| Amishnot grpmax-eligible | 11% | 9 |
| Middle Eastern | 10.1% | 10 |
| Finnishnot grpmax-eligible | 9.84% | 10 |
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
- PNPLA2
- Protein
- p.Pro486=
- Coding
- c.1458C>T
- MANE Select
- NM_020376
- dbSNP
- rs1138694
- Type
- single nucleotide variant
- Location
- chr11:824805 (GRCh38)
- Gene constraint
- LOEUF 1.221 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 72.56
- Residue 486
- the 'disordered' region
Disease context
neutral lipid storage myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatmentsFor Neutral lipid storage disease with myopathy (Orphanet):
- Inheritance
- Autosomal recessive
- Onset
- Adult
Similar variants
- PNPLA2 p.Pro486Arg Uncertain significance ★★ ⚠ same residue
- PNPLA2 p.Pro486His Uncertain significance ★★ ⚠ same residue
- PNPLA2 p.Pro486Ser Uncertain significance ★ ⚠ same residue
- PNPLA2 p.Pro486_Leu487= Likely benign ★★ same residue
- PNPLA2 c.187+1G>C Pathogenic/Likely pathogenic ★★ same condition
- PNPLA2 c.757+1G>T Pathogenic ★★ same condition
- PNPLA2 p.Arg221Pro Pathogenic ★★ same condition
- PNPLA2 p.Pro195Leu 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/pnpla2-p-pro486 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown