Is PEX3 p.Thr282Pro (c.844A>C) pathogenic?

PEX3 p.Thr282Pro (c.844A>C) is classified Likely pathogenic in PEX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-11-04). AlphaMissense: likely pathogenic (0.6365); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 10A (Zellweger).

What condition is associated with PEX3 p.Thr282Pro (c.844A>C)?

PEX3 p.Thr282Pro (c.844A>C) is associated with peroxisome biogenesis disorder 10A (Zellweger) (ClinVar).

How common is PEX3 p.Thr282Pro (c.844A>C) in the general population?

PEX3 p.Thr282Pro (c.844A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX3 p.Thr282Pro (c.844A>C)?

AlphaMissense predicts likely pathogenic (score 0.6365) — an in-silico prediction, not a clinical call.

PEX3 p.Thr282Pro

c.844A>C · rs1473197986 · VCV1065621

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6365 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 10A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.6365	likely pathogenic ✓ concordant with ClinVar
REVEL	0.219	benign-leaning
SaProt	LLR -10.89	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 38 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	23.5	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: PEX3
Protein: p.Thr282Pro
Coding: c.844A>C
MANE Select: NM_003630
dbSNP: rs1473197986
Type: single nucleotide variant
Location: chr6:143479101 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 282: an α-helix

Full PEX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 10A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX3 c.-96G>T Uncertain significance ★★ same condition
PEX3 p.Arg300Gln Uncertain significance ★★ ⚠ same condition
PEX3 p.Asp305Glu Uncertain significance ★★ ⚠ same condition
PEX3 p.Glu266Asp Uncertain significance ★★ ⚠ same condition
PEX3 p.Met270Ile Uncertain significance ★★ ⚠ same condition
PEX3 c.524-19T>C Benign ★★ same condition
PEX3 c.942-13A>G Benign ★★ same condition

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/pex3-p-thr282pro (accessed [today's date]).

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