Is PPARG p.Asp66= (c.198C>T) pathogenic?

PPARG p.Asp66= (c.198C>T) is classified Uncertain significance in PPARG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Ultra-rare (popmax 0.012%, afr); Associated with INSULIN RESISTANCE, DIGENIC.

What condition is associated with PPARG p.Asp66= (c.198C>T)?

PPARG p.Asp66= (c.198C>T) is associated with INSULIN RESISTANCE, DIGENIC, obesity disorder, PPARG-related familial partial lipodystrophy (ClinVar).

How common is PPARG p.Asp66= (c.198C>T) in the general population?

PPARG p.Asp66= (c.198C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

PPARG p.Asp66=

c.198C>T · rs753817211 · VCV342921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Conditions

INSULIN RESISTANCE, DIGENIC

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 1.1	GERP -0.038, phastCons 1
Overall
CADD	11.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.012% African / African-American · 9/74,772 alleles

Filtering AF 0.00625% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00168% 27/1,608,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,308
Remaining individualsnot grpmax-eligible	0.00321%	31,162
European (non-Finnish)	0.00136%	73,468

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.Asp66=
Coding: c.198C>T
MANE Select: NM_138711
dbSNP: rs753817211
Type: single nucleotide variant
Location: chr3:12379909 (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

INSULIN RESISTANCE, DIGENIC — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: obesity disorder 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-asp66 (accessed [today's date]).

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