Is PPARA p.Pro13= (c.39A>G) pathogenic?

PPARA p.Pro13= (c.39A>G) is classified Likely benign in PPARA (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-07). Ultra-rare (popmax 0.0217%, nfe); Associated with PPARA-related disorder.

What condition is associated with PPARA p.Pro13= (c.39A>G)?

PPARA p.Pro13= (c.39A>G) is associated with PPARA-related disorder (ClinVar).

How common is PPARA p.Pro13= (c.39A>G) in the general population?

PPARA p.Pro13= (c.39A>G) is ultra-rare (popmax 0.0217%, nfe) (gnomAD).

PPARA p.Pro13=

c.39A>G · rs117490878 · VCV3047077

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, nfe)

Conditions

PPARA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -11
Overall
CADD	0.056	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% European (non-Finnish) · 256/1,179,830 alleles

Filtering AF 0.0195% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0186%

Overall 0.017% 275/1,613,428 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0217%	4,609
Finnishnot grpmax-eligible	0.0203%	4,914
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed American	0.00167%	59,930
African / African-American	0.00134%	74,826

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: PPARA
Protein: p.Pro13=
Coding: c.39A>G
MANE Select: NM_005036
dbSNP: rs117490878
Type: single nucleotide variant
Location: chr22:46198422 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.18 · 79 PDB

Full PPARA gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

PPARA-related disorder

Similar variants

PPARA p.Pro13Thr Uncertain significance ★ ⚠ same residue
PPARA p.Ala268Val Likely benign same condition
PPARA p.Asn235= Benign ★★ same type
PPARA p.Leu184= Benign ★★ same type
PPARA p.Val227Ala Benign ★★ same type
PPARA p.Ala186Val Uncertain significance ★ same type
PPARA p.Ala201Thr Uncertain significance ★ ⚠ same type
PPARA p.Ala225Thr Uncertain significance ★ ⚠ same type

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/ppara-p-pro13 (accessed [today's date]).

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