Is PPARG p.Leu92Pro (c.275T>C) pathogenic?

PPARG p.Leu92Pro (c.275T>C) is classified Conflicting classifications of pathogenicity in PPARG (ClinVar, No assertion criteria, 2 submitters; last evaluated 2024-06-14). AlphaMissense: likely benign (0.0738); Absent from gnomAD v4.1; Associated with PPARG-related disorder.

What condition is associated with PPARG p.Leu92Pro (c.275T>C)?

PPARG p.Leu92Pro (c.275T>C) is associated with PPARG-related disorder, PPARG-related familial partial lipodystrophy (ClinVar).

How common is PPARG p.Leu92Pro (c.275T>C) in the general population?

PPARG p.Leu92Pro (c.275T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPARG p.Leu92Pro (c.275T>C)?

AlphaMissense predicts likely benign (score 0.0738) — an in-silico prediction, not a clinical call.

PPARG p.Leu92Pro

c.275T>C · VCV3345678

Conflicting classifications of pathogenicity No assertion criteria

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0738 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

PPARG-related disorder

Computational evidence

Protein change
AlphaMissense	0.0738	likely benign
REVEL	0.437	indeterminate
SaProt	LLR -6.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,711 bp · p 0.78 · regional, not allelic
Overall
CADD	22.5	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 L122P vs ClinVar L92P) — 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.Leu92Pro
Coding: c.275T>C
MANE Select: NM_138711
Type: single nucleotide variant
Location: chr3:12381376 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 321 PDB

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

Disease context

PPARG-related disorder

Also linked: PPARG-related familial partial lipodystrophy

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-leu92pro (accessed [today's date]).

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