Is PEX1 p.Pro1025Ala (c.3073C>G) pathogenic?

PEX1 p.Pro1025Ala (c.3073C>G) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-08-15). AlphaMissense: likely benign (0.0975); Absent from gnomAD v4.1.

How common is PEX1 p.Pro1025Ala (c.3073C>G) in the general population?

PEX1 p.Pro1025Ala (c.3073C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX1 p.Pro1025Ala (c.3073C>G)?

AlphaMissense predicts likely benign (score 0.0975) — an in-silico prediction, not a clinical call.

PEX1 p.Pro1025Ala

c.3073C>G · rs746345275 · VCV593671

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0975	likely benign
REVEL	0.42	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 9.7	GERP 3.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	21.0	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: PEX1
Protein: p.Pro1025Ala
Coding: c.3073C>G
MANE Select: NM_021167 · reported on NM_000466
dbSNP: rs746345275
Type: single nucleotide variant
Location: chr7:92493087 (GRCh38)

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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-pro1025ala (accessed [today's date]).

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