Is PPARG p.Asp3Asn (c.7G>A) pathogenic?

PPARG p.Asp3Asn (c.7G>A) is classified Uncertain significance in PPARG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.3342); Ultra-rare (popmax 0.0164%, mid); Associated with PPARG-related disorder.

What condition is associated with PPARG p.Asp3Asn (c.7G>A)?

PPARG p.Asp3Asn (c.7G>A) is associated with PPARG-related disorder (ClinVar).

How common is PPARG p.Asp3Asn (c.7G>A) in the general population?

PPARG p.Asp3Asn (c.7G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about PPARG p.Asp3Asn (c.7G>A)?

AlphaMissense predicts likely benign (score 0.3342) — an in-silico prediction, not a clinical call.

PPARG p.Asp3Asn

c.7G>A · VCV3356831

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3342 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

PPARG-related disorder

Computational evidence

Protein change
AlphaMissense	0.3342	likely benign
REVEL	0.254	benign-leaning
SaProt	LLR -6.47	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 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 1,711 bp · p 0.78 · regional, not allelic
Overall
CADD	29.1	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 D33N vs ClinVar D3N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,798 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
Remaining individualsnot grpmax-eligible	0.0016%	62,472
European (non-Finnish)	0.00017%	589,957

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.Asp3Asn
Coding: c.7G>A
MANE Select: NM_138711
Type: single nucleotide variant
Location: chr3:12379718 (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

PPARG-related disorder

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-asp3asn (accessed [today's date]).

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