Is PPARG p.Ser156fs (c.466del) pathogenic?

PPARG p.Ser156fs (c.466del) is classified Pathogenic in PPARG (ClinVar, No assertion criteria, 1 submitter; last evaluated 1999-06-01). Very rare (popmax 8.48e-05%, nfe); Associated with colon carcinoma.

What condition is associated with PPARG p.Ser156fs (c.466del)?

PPARG p.Ser156fs (c.466del) is associated with colon carcinoma (ClinVar).

How common is PPARG p.Ser156fs (c.466del) in the general population?

PPARG p.Ser156fs (c.466del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

PPARG p.Ser156fs

c.466del · rs587776687 · VCV8132

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

colon carcinoma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.2	GERP -0.93, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,802 alleles

Overall 0.000137% 2/1,461,568 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,966
European (non-Finnish)grpmax	8.48e-05%	1,179,802

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser156fs
Coding: c.466del
MANE Select: NM_138711
dbSNP: rs587776687
Type: Deletion
Location: chr3:12392683 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 321 PDB
Residue 156: a DNA-binding region

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

Disease context

colon carcinoma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPARG p.Ser156Gly Uncertain significance ★ ⚠ same residue
PPARG p.Arg286His Uncertain significance ★ same condition
PPARG p.Gln284Pro Pathogenic same condition
PPARG p.Lys317Ter Pathogenic same condition
PPARG p.Pro424fs Pathogenic ★★ same type
PPARG c.-8-28082del Likely pathogenic ★ same type
PPARG p.Ala276fs Likely pathogenic ★ same type
PPARG p.Ser17fs Likely pathogenic ★ same type

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-ser156fs (accessed [today's date]).

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