Is PNPLA2 p.Ser372= (c.1116C>T) pathogenic?

PNPLA2 p.Ser372= (c.1116C>T) is classified Likely benign in PNPLA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-02). Very rare (popmax 0.00977%, amr); Associated with neutral lipid storage myopathy.

What condition is associated with PNPLA2 p.Ser372= (c.1116C>T)?

PNPLA2 p.Ser372= (c.1116C>T) is associated with neutral lipid storage myopathy (ClinVar).

How common is PNPLA2 p.Ser372= (c.1116C>T) in the general population?

PNPLA2 p.Ser372= (c.1116C>T) is very rare (popmax 0.00977%, amr) (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.Ser372=

c.1116C>T · rs768832340 · VCV1606026

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00977%, amr)

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 0.26	GERP 0.49, phastCons 0.98
Overall
CADD	9.017	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00977% Admixed American · 5/51,162 alleles

Filtering AF 0.00381% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00247%

Overall 0.000322% 5/1,551,398 alleles · very rare exomes 5/1,399,110 · genomes 0/152,288 · 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: PNPLA2
Protein: p.Ser372=
Coding: c.1116C>T
MANE Select: NM_020376
dbSNP: rs768832340
Type: single nucleotide variant
Location: chr11:824377 (GRCh38)
Gene constraint: LOEUF 1.221 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.56
Residue 372: a modified residue (phosphoserine; in vitro)

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 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
PNPLA2 p.Ala263Ser Uncertain significance ★★ ⚠ same condition
PNPLA2 p.Ala263Thr 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-ser372 (accessed [today's date]).

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