Is PPARA p.Asp328= (c.984C>T) pathogenic?

PPARA p.Asp328= (c.984C>T) is classified Likely benign in PPARA (ClinVar, Single submitter, 1 submitter; last evaluated 2018-07-20). Very rare (popmax 0.004%, afr).

How common is PPARA p.Asp328= (c.984C>T) in the general population?

PPARA p.Asp328= (c.984C>T) is very rare (popmax 0.004%, afr) (gnomAD).

PPARA p.Asp328=

c.984C>T · rs917522785 · VCV766219

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

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 -13	GERP -4.2
Overall
CADD	8.31	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,028 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000805% 13/1,614,142 alleles · very rare exomes 13/1,461,894 · genomes 0/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,009
South Asian	0.0022%	45,544
European (non-Finnish)	0.000678%	147,503

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.Asp328=
Coding: c.984C>T
MANE Select: NM_005036
dbSNP: rs917522785
Type: single nucleotide variant
Location: chr22:46232064 (GRCh38)
Gene constraint: LOEUF 0.711 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.18 · 79 PDB
Residue 328: the nr lbd domain; the 'required for heterodimerization with rxra' region

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

Similar variants

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
PPARA p.Ala291Thr Uncertain significance ★ ⚠ same type
PPARA p.Ala381Pro 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-asp328 (accessed [today's date]).

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