Is PPARD p.Met403Thr (c.1208T>C) pathogenic?

PPARD p.Met403Thr (c.1208T>C) is classified Uncertain significance in PPARD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-18). AlphaMissense: likely pathogenic (0.8185); Absent from gnomAD v4.1.

How common is PPARD p.Met403Thr (c.1208T>C) in the general population?

PPARD p.Met403Thr (c.1208T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PPARD p.Met403Thr (c.1208T>C)?

AlphaMissense predicts likely pathogenic (score 0.8185) — an in-silico prediction, not a clinical call.

PPARD p.Met403Thr

c.1208T>C · VCV3936468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8185 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8185	likely pathogenic
REVEL	0.874	moderately pathogenic-leaning
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 15 kb · p 2.9e-16 · 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.

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: PPARD
Protein: p.Met403Thr
Coding: c.1208T>C
MANE Select: NM_006238
Type: single nucleotide variant
Location: chr6:35425961 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.65 · 56 PDB
Residue 403: the nr lbd domain; an α-helix

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

Similar variants

PPARD p.Ala158Val Uncertain significance ★ ⚠ same type
PPARD p.Ala209Val Uncertain significance ★ ⚠ same type
PPARD p.Ala21Pro Uncertain significance ★ ⚠ same type
PPARD p.Ala292Thr Uncertain significance ★ ⚠ same type
PPARD p.Ala392Asp Uncertain significance ★ ⚠ same type
PPARD p.Arg103His Uncertain significance ★ ⚠ same type
PPARD p.Arg113His Uncertain significance ★ ⚠ same type
PPARD p.Arg12Trp 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/ppard-p-met403thr (accessed [today's date]).

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