Is PEX1 p.Pro162Ser (c.484C>T) pathogenic?

PEX1 p.Pro162Ser (c.484C>T) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-17). AlphaMissense: likely pathogenic (0.5928); Very rare (popmax 6.84e-05%).

How common is PEX1 p.Pro162Ser (c.484C>T) in the general population?

PEX1 p.Pro162Ser (c.484C>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about PEX1 p.Pro162Ser (c.484C>T)?

AlphaMissense predicts likely pathogenic (score 0.5928) — an in-silico prediction, not a clinical call.

PEX1 p.Pro162Ser

c.484C>T · rs2116247732 · VCV1205410

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5928 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5928	likely pathogenic
REVEL	0.831	moderately pathogenic-leaning
SaProt	LLR -11.73	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	24.2	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

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,814 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PEX1
Protein: p.Pro162Ser
Coding: c.484C>T
MANE Select: NM_000466
dbSNP: rs2116247732
Type: single nucleotide variant
Location: chr7:92518031 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19

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

Similar variants

PEX1 p.Pro162Thr Likely pathogenic ★ same residue
PEX1 c.1239+1G>T Pathogenic ★★ same type
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same type
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same type
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same type
PEX1 c.1483+1G>A Pathogenic ★★ same type
PEX1 c.1587+1G>A Likely pathogenic ★★ same type
PEX1 c.1670+1G>A Pathogenic/Likely pathogenic ★★ same type

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-pro162ser (accessed [today's date]).

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