Is PEX6 p.Arg82Pro (c.245G>C) pathogenic?

PEX6 p.Arg82Pro (c.245G>C) is classified Uncertain significance in PEX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-09). AlphaMissense: likely benign (0.1485); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder.

What condition is associated with PEX6 p.Arg82Pro (c.245G>C)?

PEX6 p.Arg82Pro (c.245G>C) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX6 p.Arg82Pro (c.245G>C) in the general population?

PEX6 p.Arg82Pro (c.245G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX6 p.Arg82Pro (c.245G>C)?

AlphaMissense predicts likely benign (score 0.1485) — an in-silico prediction, not a clinical call.

PEX6 p.Arg82Pro

c.245G>C · rs2150240495 · VCV1352503

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1485 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
AlphaMissense	0.1485	likely benign
REVEL	0.59	indeterminate
SaProt	LLR -7.08	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP 0.55, phastCons 0.99
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.19 · regional, not allelic
Overall
CADD	19.03	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

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: PEX6
Protein: p.Arg82Pro
Coding: c.245G>C
MANE Select: NM_000287
dbSNP: rs2150240495
Type: single nucleotide variant
Location: chr6:42978906 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.87

Full PEX6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX6 p.Arg82= Likely benign ★ same residue
PEX6 c.1130+1G>A Likely pathogenic ★★ same condition
PEX6 c.1233+1G>A Likely pathogenic ★★ same condition
PEX6 c.1688+1G>A Pathogenic ★★ same condition
PEX6 c.1689-1G>A Likely pathogenic ★★ same condition
PEX6 c.1885-1G>A Likely pathogenic ★★ same condition
PEX6 c.1962-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX6 c.2094+1G>A Likely pathogenic ★★ 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/pex6-p-arg82pro (accessed [today's date]).

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