Is PPARG p.His447= (c.1341C>T) pathogenic?

PPARG p.His447= (c.1341C>T) is classified Benign/Likely benign in PPARG (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 20.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with obesity disorder.

What condition is associated with PPARG p.His447= (c.1341C>T)?

PPARG p.His447= (c.1341C>T) is associated with obesity disorder, PPARG-related familial partial lipodystrophy, glioma susceptibility 1 (ClinVar).

PPARG p.His447=

Q: How common is PPARG p.His447= (c.1341C>T) in the general population?

PPARG p.His447= (c.1341C>T) is common (popmax 20.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1341C>T · rs3856806 · VCV8139

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 20.1%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

obesity disorder

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 -8.2	GERP -3.3
Overall
CADD	5.078	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20.1% East Asian · 9,007/44,870 alleles

Filtering AF 19.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 19.6%

Overall 12.7% 205,067/1,614,040 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	20.1%	5
Finnishnot grpmax-eligible	19.7%	5
South Asian	14.4%	7
European (non-Finnish)	12.7%	8
Remaining individualsnot grpmax-eligible	12%	8
Admixed American	10.2%	10
Middle Eastern	8.04%	12
Ashkenazi Jewishnot grpmax-eligible	7.37%	14
African / African-American	6.08%	16
Amishnot grpmax-eligible	4.17%	24

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.His447=
Coding: c.1341C>T
MANE Select: NM_138711
dbSNP: rs3856806
Type: single nucleotide variant
Location: chr3:12434058 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 321 PDB
Residue 447: the nr lbd domain; an α-helix

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

Disease context

obesity disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: PPARG-related familial partial lipodystrophy glioma susceptibility 1

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-his447 (accessed [today's date]).

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