Is PPARG p.Arg210Gln (c.629G>A) pathogenic?

PPARG p.Arg210Gln (c.629G>A) is classified Conflicting classifications of pathogenicity in PPARG (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2023-06-27). AlphaMissense: ambiguous (0.3599); Very rare (popmax 0.00333%, amr); Associated with obesity disorder.

What condition is associated with PPARG p.Arg210Gln (c.629G>A)?

PPARG p.Arg210Gln (c.629G>A) is associated with obesity disorder, PPARG-related familial partial lipodystrophy (ClinVar).

How common is PPARG p.Arg210Gln (c.629G>A) in the general population?

PPARG p.Arg210Gln (c.629G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about PPARG p.Arg210Gln (c.629G>A)?

AlphaMissense predicts ambiguous (score 0.3599) — an in-silico prediction, not a clinical call.

PPARG p.Arg210Gln

c.629G>A · rs150296212 · VCV901923

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

ambiguous

0.3599 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

obesity disorder

Computational evidence

Protein change
AlphaMissense	0.3599	ambiguous
REVEL	0.342	indeterminate
SaProt	LLR -4.62	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.60	unconstrained · MANE · 53 kb · p 1.2e-17 · regional, not allelic
Overall
CADD	27.8	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 R240Q vs ClinVar R210Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,992 alleles

Filtering AF 0.00231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00202%

Overall 0.00266% 43/1,613,976 alleles · very rare exomes 41/1,461,840 · genomes 2/152,136 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,996
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00314%	31,892
South Asian	0.0022%	45,545

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.Arg210Gln
Coding: c.629G>A
MANE Select: NM_138711
dbSNP: rs150296212
Type: single nucleotide variant
Location: chr3:12405981 (GRCh38)
Gene constraint: LOEUF 0.628 · pLI 0.21 (gnomAD)
Structure: AlphaFold pLDDT 76.11 · 321 PDB
Residue 240 UniProt numbering: the nr lbd domain; an α-helix; the 'interaction with fam120b' region

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.Arg210Pro Likely pathogenic ★ 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-arg210gln (accessed [today's date]).

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