Is PPARA p.Ala186Val (c.557C>T) pathogenic?

PPARA p.Ala186Val (c.557C>T) is classified Uncertain significance in PPARA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-16). AlphaMissense: ambiguous (0.4877); Absent from gnomAD v4.1.

How common is PPARA p.Ala186Val (c.557C>T) in the general population?

PPARA p.Ala186Val (c.557C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPARA p.Ala186Val (c.557C>T)?

AlphaMissense predicts ambiguous (score 0.4877) — an in-silico prediction, not a clinical call.

PPARA p.Ala186Val

c.557C>T · rs1934855724 · VCV2486341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4877 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4877	ambiguous
REVEL	0.638	indeterminate
SaProt	LLR -10.03	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 20 kb · p 5.8e-13 · regional, not allelic
Overall
CADD	24.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PPARA
Protein: p.Ala186Val
Coding: c.557C>T
MANE Select: NM_005036
dbSNP: rs1934855724
Type: single nucleotide variant
Location: chr22:46219860 (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

Similar variants

PPARA p.Asn235= Benign ★★ same type
PPARA p.Leu184= Benign ★★ same type
PPARA p.Val227Ala Benign ★★ 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
PPARA p.Arg141His 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-ala186val (accessed [today's date]).

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