Is PEX1 p.Leu965Pro (c.2894T>C) pathogenic?

PEX1 p.Leu965Pro (c.2894T>C) is classified Likely pathogenic in PEX1 (ClinVar, Single submitter, 1 submitter). AlphaMissense: likely pathogenic (0.9966); Absent from gnomAD v4.1.

How common is PEX1 p.Leu965Pro (c.2894T>C) in the general population?

PEX1 p.Leu965Pro (c.2894T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX1 p.Leu965Pro (c.2894T>C)?

AlphaMissense predicts likely pathogenic (score 0.9966) — an in-silico prediction, not a clinical call.

PEX1 p.Leu965Pro

c.2894T>C · rs786205586 · VCV191221

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9966 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9966	likely pathogenic ✓ concordant with ClinVar
REVEL	0.983	strongly pathogenic-leaning
SaProt	LLR -17.86	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 3.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	32.0	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: PEX1
Protein: p.Leu965Pro
Coding: c.2894T>C
MANE Select: NM_021167 · reported on NM_000466
dbSNP: rs786205586
Type: single nucleotide variant
Location: chr7:92494519 (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-leu965pro (accessed [today's date]).

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