Is PPARG p.Ile301Val (c.901A>G) pathogenic?

PPARG p.Ile301Val (c.901A>G) is classified Uncertain significance in PPARG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-29). AlphaMissense: likely benign (0.2555); Ultra-rare (popmax 0.0274%, sas); Associated with PPARG-related disorder.

What condition is associated with PPARG p.Ile301Val (c.901A>G)?

PPARG p.Ile301Val (c.901A>G) is associated with PPARG-related disorder (ClinVar).

How common is PPARG p.Ile301Val (c.901A>G) in the general population?

PPARG p.Ile301Val (c.901A>G) is ultra-rare (popmax 0.0274%, sas) (gnomAD).

What do computational predictors say about PPARG p.Ile301Val (c.901A>G)?

AlphaMissense predicts likely benign (score 0.2555) — an in-silico prediction, not a clinical call.

PPARG p.Ile301Val

c.901A>G · VCV3353211

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2555 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0274%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

PPARG-related disorder

Computational evidence

Protein change
AlphaMissense	0.2555	likely benign
REVEL	0.344	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 53 kb · p 1.2e-17 · regional, not allelic
Overall
CADD	22.3	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 I331V vs ClinVar I301V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0274% South Asian · 25/91,086 alleles

Filtering AF 0.019% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0163%

Overall 0.00155% 25/1,614,020 alleles · ultra-rare exomes 22/1,461,854 · genomes 3/152,166 · 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.Ile301Val
Coding: c.901A>G
MANE Select: NM_138711
Type: single nucleotide variant
Location: chr3:12416875 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 321 PDB
Residue 331 UniProt numbering: the nr lbd domain

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-ile301val (accessed [today's date]).

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