Is PPARG p.Val288Met (c.862G>A) pathogenic?

PPARG p.Val288Met (c.862G>A) is classified Pathogenic in PPARG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2003-04-01). AlphaMissense: likely pathogenic (0.8189); Very rare (popmax 8.47e-05%, nfe); Associated with PPARG-related familial partial lipodystrophy.

What condition is associated with PPARG p.Val288Met (c.862G>A)?

PPARG p.Val288Met (c.862G>A) is associated with PPARG-related familial partial lipodystrophy (ClinVar).

How common is PPARG p.Val288Met (c.862G>A) in the general population?

PPARG p.Val288Met (c.862G>A) is very rare (popmax 8.47e-05%, nfe) (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.Val288Met (c.862G>A)?

AlphaMissense predicts likely pathogenic (score 0.8189) — an in-silico prediction, not a clinical call.

PPARG p.Val288Met

c.862G>A · rs72551362 · VCV8137

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8189 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

PPARG-related familial partial lipodystrophy

Computational evidence

Protein change
AlphaMissense	0.8189	likely pathogenic ✓ concordant with ClinVar
REVEL	0.534	indeterminate
SaProt	LLR -8.47	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 53 kb · p 1.2e-17 · regional, not allelic
Overall
CADD	28.9	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 V318M vs ClinVar V288M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,022 alleles

Overall 6.2e-05% 1/1,614,154 alleles · very rare exomes 1/1,461,838 · genomes 0/152,316 · 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: PPARG
Protein: p.Val288Met
Coding: c.862G>A
MANE Select: NM_138711
dbSNP: rs72551362
Type: single nucleotide variant
Location: chr3:12416836 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 321 PDB
Residue 318 UniProt numbering: the nr lbd domain; a UniProt-annotated variant site (in diabetes); an α-helix

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

Disease context

PPARG-related familial partial lipodystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-val288met (accessed [today's date]).

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