Is PPARG p.Pro10Ala (c.28C>G) pathogenic?

PPARG p.Pro10Ala (c.28C>G) is classified Benign in PPARG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2007-06-01). AlphaMissense: likely benign (0.1206); Absent from gnomAD v4.1; Associated with Diabetes mellitus, noninsulin-dependent, modifier of.

What condition is associated with PPARG p.Pro10Ala (c.28C>G)?

PPARG p.Pro10Ala (c.28C>G) is associated with Diabetes mellitus, noninsulin-dependent, modifier of (ClinVar).

How common is PPARG p.Pro10Ala (c.28C>G) in the general population?

PPARG p.Pro10Ala (c.28C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPARG p.Pro10Ala (c.28C>G)?

AlphaMissense predicts likely benign (score 0.1206) — an in-silico prediction, not a clinical call.

PPARG p.Pro10Ala

c.28C>G · rs1805192 · VCV8131

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1206 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Diabetes mellitus, noninsulin-dependent, modifier of

Computational evidence

Protein change
AlphaMissense	0.1206	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -7.25	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 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,711 bp · p 0.78 · regional, not allelic
Overall
CADD	23.2	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 P40A vs ClinVar P10A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPARG
Protein: p.Pro10Ala
Coding: c.28C>G
MANE Select: NM_138711
dbSNP: rs1805192
Type: single nucleotide variant
Location: chr3:12379739 (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

Diabetes mellitus, noninsulin-dependent, modifier of

Similar variants

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
PPARG p.Leu450Pro 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-pro10ala (accessed [today's date]).

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