Is PPARG p.Thr45Ala (c.133A>G) pathogenic?

PPARG p.Thr45Ala (c.133A>G) is classified Likely benign in PPARG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely benign (0.0546); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with PPARG p.Thr45Ala (c.133A>G)?

PPARG p.Thr45Ala (c.133A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PPARG p.Thr45Ala (c.133A>G) in the general population?

PPARG p.Thr45Ala (c.133A>G) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about PPARG p.Thr45Ala (c.133A>G)?

AlphaMissense predicts likely benign (score 0.0546) — an in-silico prediction, not a clinical call.

PPARG p.Thr45Ala

c.133A>G · rs201978569 · VCV3217014

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0546 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0546	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.5	GERP -3.5
Regional constraint	o/e 1.02	unconstrained · MANE · 1,711 bp · p 0.78 · regional, not allelic
Overall
CADD	0.055	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 T75A vs ClinVar T45A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,862 alleles

Overall 0.000124% 2/1,613,798 alleles · very rare exomes 2/1,461,648 · genomes 0/152,150 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,862
European (non-Finnish)	8.48e-05%	1,179,820

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.Thr45Ala
Coding: c.133A>G
MANE Select: NM_138711
dbSNP: rs201978569
Type: single nucleotide variant
Location: chr3:12379844 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPARG p.Thr45Pro Uncertain significance ★ ⚠ same residue
PPARG c.-8A>G Uncertain significance ★★ ⚠ same condition
PPARG p.Thr54Pro Uncertain significance ★★ ⚠ same condition
PPARG p.Val291Leu Uncertain significance ★★ ⚠ same condition
PPARG c.1181-6C>T Uncertain significance ★ same condition
PPARG c.-8-28053C>G Uncertain significance ★ ⚠ same condition
PPARG p.Arg157Lys Uncertain significance ★ ⚠ same condition
PPARG p.Asn102Thr 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-thr45ala (accessed [today's date]).

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