Is PPARG p.Ser380= (c.1140C>T) pathogenic?

PPARG p.Ser380= (c.1140C>T) is classified Likely benign in PPARG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-17). Ultra-rare (popmax 0.0198%, sas); Associated with PPARG-related disorder.

What condition is associated with PPARG p.Ser380= (c.1140C>T)?

PPARG p.Ser380= (c.1140C>T) is associated with PPARG-related disorder (ClinVar).

How common is PPARG p.Ser380= (c.1140C>T) in the general population?

PPARG p.Ser380= (c.1140C>T) is ultra-rare (popmax 0.0198%, sas) (gnomAD).

PPARG p.Ser380=

c.1140C>T · rs148844673 · VCV3048704

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0198%, sas)

Conditions

PPARG-related 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 -1.6	GERP -4.4
Overall
CADD	9.58	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0198% South Asian · 18/91,074 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0106%

Overall 0.00229% 37/1,614,014 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0198%	5,060
Middle Eastern	0.0165%	6,060
East Asian	0.00223%	44,878
Admixed American	0.00167%	60,016
Remaining individualsnot grpmax-eligible	0.0016%	62,498
European (non-Finnish)	0.00127%	78,664

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.Ser380=
Coding: c.1140C>T
MANE Select: NM_138711
dbSNP: rs148844673
Type: single nucleotide variant
Location: chr3:12417114 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 321 PDB
Residue 380: the nr lbd domain; an α-helix

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

Disease context

PPARG-related disorder

Similar variants

PPARG p.Ser380Arg Uncertain significance ★★ ⚠ same residue
PPARG p.Pro83Gln Uncertain significance ★★ ⚠ same condition
PPARG p.Tyr143Cys Uncertain significance ★★ ⚠ same condition
PPARG p.Val111Ile Uncertain significance ★★ same condition
PPARG c.730-2A>G Likely pathogenic ★ same condition
PPARG p.Gln435Ter Likely pathogenic ★ same condition
PPARG p.Arg134Pro Uncertain significance ★ ⚠ same condition
PPARG p.Arg286His 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-ser380 (accessed [today's date]).

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