Is PPARG p.Asp19Ala (c.56A>C) pathogenic?

PPARG p.Asp19Ala (c.56A>C) is classified Uncertain significance in PPARG (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely benign (0.2744); Very rare (popmax 0.00167%, amr); Associated with obesity disorder.

What condition is associated with PPARG p.Asp19Ala (c.56A>C)?

PPARG p.Asp19Ala (c.56A>C) is associated with obesity disorder, PPARG-related familial partial lipodystrophy (ClinVar).

How common is PPARG p.Asp19Ala (c.56A>C) in the general population?

PPARG p.Asp19Ala (c.56A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about PPARG p.Asp19Ala (c.56A>C)?

AlphaMissense predicts likely benign (score 0.2744) — an in-silico prediction, not a clinical call.

PPARG p.Asp19Ala

c.56A>C · rs762280243 · VCV901544

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2744 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

obesity disorder

Computational evidence

Protein change
AlphaMissense	0.2744	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -8.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,711 bp · p 0.78 · regional, not allelic
Overall
CADD	26.1	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 D49A vs ClinVar D19A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,996 alleles

Overall 6.2e-05% 1/1,614,016 alleles · very rare exomes 1/1,461,736 · genomes 0/152,280 · joint denominator

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.Asp19Ala
Coding: c.56A>C
MANE Select: NM_138711
dbSNP: rs762280243
Type: single nucleotide variant
Location: chr3:12379767 (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

obesity disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: PPARG-related familial partial lipodystrophy

Similar variants

PPARG p.Asp19Glu Uncertain significance ★ ⚠ same residue
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

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-asp19ala (accessed [today's date]).

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