Is PEX1 p.Ser98Phe (c.293C>T) pathogenic?

PEX1 p.Ser98Phe (c.293C>T) is classified Conflicting classifications of pathogenicity in PEX1 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-08-30). AlphaMissense: likely benign (0.1373); Ultra-rare (popmax 0.0455%, afr); Associated with Inborn genetic diseases.

What condition is associated with PEX1 p.Ser98Phe (c.293C>T)?

PEX1 p.Ser98Phe (c.293C>T) is associated with Inborn genetic diseases, Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Ser98Phe (c.293C>T) in the general population?

PEX1 p.Ser98Phe (c.293C>T) is ultra-rare (popmax 0.0455%, afr) (gnomAD).

What do computational predictors say about PEX1 p.Ser98Phe (c.293C>T)?

AlphaMissense predicts likely benign (score 0.1373) — an in-silico prediction, not a clinical call.

PEX1 p.Ser98Phe

c.293C>T · rs369100815 · VCV288355

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1373 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0455%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1373	likely benign
REVEL	0.56	indeterminate
SaProt	LLR -7.29	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 1.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	20.9	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

Grpmax group 0.0455% African / African-American · 34/74,740 alleles

Filtering AF 0.0334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00212% 34/1,606,254 alleles · ultra-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.Ser98Phe
Coding: c.293C>T
MANE Select: NM_000466
dbSNP: rs369100815
Type: single nucleotide variant
Location: chr7:92519059 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Zellweger spectrum disorders

Similar variants

PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely 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.1483+1G>A Pathogenic ★★ same condition
PEX1 c.1587+1G>A Likely pathogenic ★★ same condition
PEX1 c.1670+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1670+1G>T 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-ser98phe (accessed [today's date]).

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