Is PPARG p.Asp50His (c.148G>C) pathogenic?

PPARG p.Asp50His (c.148G>C) is classified Uncertain significance in PPARG (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.24); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PPARG p.Asp50His (c.148G>C)?

PPARG p.Asp50His (c.148G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PPARG p.Asp50His (c.148G>C) in the general population?

PPARG p.Asp50His (c.148G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPARG p.Asp50His (c.148G>C)?

AlphaMissense predicts likely benign (score 0.24) — an in-silico prediction, not a clinical call.

PPARG p.Asp50His

c.148G>C · VCV4142161

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.24 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.24	likely benign
REVEL	0.213	benign-leaning
SaProt	LLR -6.96	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 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,711 bp · p 0.78 · regional, not allelic
Overall
CADD	22.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM D80H vs ClinVar D50H) — 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.Asp50His
Coding: c.148G>C
MANE Select: NM_138711
Type: single nucleotide variant
Location: chr3:12379859 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PPARG p.Asp50= Conflicting classifications of pathogenicity ★ same residue
PPARG c.-8A>G Uncertain significance ★★ ⚠ same condition
PPARG p.Thr54Pro Uncertain significance ★★ ⚠ same condition
PPARG p.Val291Leu Uncertain significance ★★ ⚠ same condition
PPARG c.1181-6C>T Uncertain significance ★ same condition
PPARG c.-8-28053C>G Uncertain significance ★ ⚠ same condition
PPARG p.Arg157Lys Uncertain significance ★ ⚠ same condition
PPARG p.Asn102Thr 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-asp50his (accessed [today's date]).

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