Is PPARD p.Arg12Trp (c.34C>T) pathogenic?

PPARD p.Arg12Trp (c.34C>T) is classified Uncertain significance in PPARD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-03). AlphaMissense: likely benign (0.1352); Very rare (popmax 0.00904%, nfe).

How common is PPARD p.Arg12Trp (c.34C>T) in the general population?

PPARD p.Arg12Trp (c.34C>T) is very rare (popmax 0.00904%, nfe) (gnomAD).

What do computational predictors say about PPARD p.Arg12Trp (c.34C>T)?

AlphaMissense predicts likely benign (score 0.1352) — an in-silico prediction, not a clinical call.

PPARD p.Arg12Trp

c.34C>T · rs200600159 · VCV2411595

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1352 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00904%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1352	likely benign
REVEL	0.484	indeterminate
SaProt	LLR -7.98	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 15 kb · p 2.9e-16 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00904% European (non-Finnish) · 105/1,161,530 alleles

Filtering AF 0.00761% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00711%

Overall 0.00728% 115/1,579,356 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00904%	11,062
African / African-American	0.00546%	18,304
Remaining individualsnot grpmax-eligible	0.00329%	30,428
Finnishnot grpmax-eligible	0.00316%	31,598
East Asian	0.00238%	42,104
South Asian	0.00115%	86,626

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: PPARD
Protein: p.Arg12Trp
Coding: c.34C>T
MANE Select: NM_006238
dbSNP: rs200600159
Type: single nucleotide variant
Location: chr6:35411121 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 83.65 · 56 PDB
Residue 12: the 'disordered' region

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.Arg318His 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-arg12trp (accessed [today's date]).

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