Is PEX1 p.Leu722Pro (c.2165T>C) pathogenic?

PEX1 p.Leu722Pro (c.2165T>C) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-06-11). AlphaMissense: likely pathogenic (0.7322); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder.

What condition is associated with PEX1 p.Leu722Pro (c.2165T>C)?

PEX1 p.Leu722Pro (c.2165T>C) is associated with peroxisome biogenesis disorder (ClinVar).

How common is PEX1 p.Leu722Pro (c.2165T>C) in the general population?

PEX1 p.Leu722Pro (c.2165T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX1 p.Leu722Pro (c.2165T>C)?

AlphaMissense predicts likely pathogenic (score 0.7322) — an in-silico prediction, not a clinical call.

PEX1 p.Leu722Pro

c.2165T>C · rs2484664903 · VCV1805623

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7322 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder

Computational evidence

Protein change
AlphaMissense	0.7322	likely pathogenic
REVEL	0.906	moderately pathogenic-leaning
SaProt	LLR -17.31	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 4.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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: PEX1
Protein: p.Leu722Pro
Coding: c.2165T>C
MANE Select: NM_000466
dbSNP: rs2484664903
Type: single nucleotide variant
Location: chr7:92503102 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 722: a UniProt-annotated variant site (in pbd1a)

Full PEX1 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

PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1670+1G>T Pathogenic ★★ same condition
PEX1 c.1900+2T>C Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.2071+1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same condition
PEX1 p.Arg633Ter 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/pex1-p-leu722pro (accessed [today's date]).

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