Is PPARG p.Phe372Leu (c.1116C>A) pathogenic?

PPARG p.Phe372Leu (c.1116C>A) is classified Uncertain significance in PPARG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.9815); Absent from gnomAD v4.1; Associated with PPARG-related familial partial lipodystrophy.

What condition is associated with PPARG p.Phe372Leu (c.1116C>A)?

PPARG p.Phe372Leu (c.1116C>A) is associated with PPARG-related familial partial lipodystrophy, obesity disorder (ClinVar).

How common is PPARG p.Phe372Leu (c.1116C>A) in the general population?

PPARG p.Phe372Leu (c.1116C>A) is absent from gnomAD v4.1 (gnomAD).

How is PPARG-related familial partial lipodystrophy inherited?

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

What do computational predictors say about PPARG p.Phe372Leu (c.1116C>A)?

AlphaMissense predicts likely pathogenic (score 0.9815) — an in-silico prediction, not a clinical call.

PPARG p.Phe372Leu

c.1116C>A · rs886057902 · VCV343048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9815 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PPARG-related familial partial lipodystrophy

Computational evidence

Protein change
AlphaMissense	0.9815	likely pathogenic
REVEL	0.716	pathogenic-leaning
SaProt	LLR -5.87	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 2.3, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 53 kb · p 1.2e-17 · regional, not allelic
Overall
CADD	26.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F402L vs ClinVar F372L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPARG
Protein: p.Phe372Leu
Coding: c.1116C>A
MANE Select: NM_138711
dbSNP: rs886057902
Type: single nucleotide variant
Location: chr3:12417090 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 321 PDB
Residue 402 UniProt numbering: the nr lbd domain; an α-helix

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

Disease context

Also linked: obesity disorder

For PPARG-related familial partial lipodystrophy (Orphanet):

Inheritance: Autosomal dominant
Onset: Adult

Similar variants

PPARG p.Arg164Gln Likely pathogenic ★★ same condition
PPARG p.Arg395Cys Pathogenic/Likely pathogenic ★★ same condition
PPARG p.Arg395His Pathogenic/Likely pathogenic ★★ same condition
PPARG p.Pro465Leu Pathogenic/Likely pathogenic ★★ same condition
PPARG p.Tyr121Cys Pathogenic/Likely pathogenic ★★ same condition
PPARG p.Asp144Gly Uncertain significance ★★ ⚠ same condition
PPARG p.Met105Ile Uncertain significance ★★ ⚠ same condition
PPARG p.Pro83Gln 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/pparg-p-phe372leu (accessed [today's date]).

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