Is PNPLA2 p.Arg120= (c.360C>T) pathogenic?

PNPLA2 p.Arg120= (c.360C>T) is classified Likely benign in PNPLA2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-26). Ultra-rare (popmax 0.0627%, afr); Associated with neutral lipid storage myopathy.

What condition is associated with PNPLA2 p.Arg120= (c.360C>T)?

PNPLA2 p.Arg120= (c.360C>T) is associated with neutral lipid storage myopathy (ClinVar).

How common is PNPLA2 p.Arg120= (c.360C>T) in the general population?

PNPLA2 p.Arg120= (c.360C>T) is ultra-rare (popmax 0.0627%, afr) (gnomAD).

How is Neutral lipid storage disease with myopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

PNPLA2 p.Arg120=

c.360C>T · rs141674273 · VCV465793

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0627%, afr)

Conditions

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 -12	GERP -4.3
Overall
CADD	0.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0627% African / African-American · 47/74,912 alleles

Filtering AF 0.0484% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0433%

Overall 0.00867% 140/1,613,838 alleles · ultra-rare exomes 107/1,461,644 · genomes 33/152,194 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0627%	1,594
Middle Eastern	0.0329%	3,042
Remaining individualsnot grpmax-eligible	0.0176%	5,680
Admixed American	0.0133%	7,501
European (non-Finnish)	0.0061%	16,389

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.Arg120=
Coding: c.360C>T
MANE Select: NM_020376
dbSNP: rs141674273
Type: single nucleotide variant
Location: chr11:821800 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.56
Residue 120: the pnpla domain

Full PNPLA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neutral lipid storage myopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Neutral lipid storage disease with myopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

Similar variants

PNPLA2 p.Arg120Cys Uncertain significance ★★ ⚠ same residue
PNPLA2 p.Arg120His Uncertain significance ★★ ⚠ 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
PNPLA2 c.1175+3G>A Uncertain significance ★★ same condition
PNPLA2 c.*383C>T Uncertain significance ★★ 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-arg120 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown