Is PEX2 p.Arg94Ser (c.282A>T) pathogenic?

PEX2 p.Arg94Ser (c.282A>T) is classified Conflicting classifications of pathogenicity in PEX2 (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2024-12-09). AlphaMissense: likely benign (0.1109); Rare (popmax 0.102%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX2 p.Arg94Ser (c.282A>T)?

PEX2 p.Arg94Ser (c.282A>T) is associated with Inborn genetic diseases, peroxisome biogenesis disorder 5A (Zellweger), peroxisome biogenesis disorder 5B (ClinVar).

How common is PEX2 p.Arg94Ser (c.282A>T) in the general population?

PEX2 p.Arg94Ser (c.282A>T) is rare (popmax 0.102%, nfe) (gnomAD).

What do computational predictors say about PEX2 p.Arg94Ser (c.282A>T)?

AlphaMissense predicts likely benign (score 0.1109) — an in-silico prediction, not a clinical call.

PEX2 p.Arg94Ser

c.282A>T · rs140963177 · VCV596242

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.1109 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.102%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1109	likely benign
REVEL	0.221	benign-leaning
SaProt	LLR -4.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.5	GERP -4.5
Regional constraint	o/e 0.99	unconstrained · MANE · 914 bp · p 0.85 · regional, not allelic
Overall
CADD	1.139	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 0.102% European (non-Finnish) · 1,203/1,180,010 alleles

Filtering AF 0.0971% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0952%

Overall 0.0792% 1,279/1,614,038 alleles · rare exomes 1,215/1,461,864 · genomes 64/152,174 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.102%	981
Remaining individualsnot grpmax-eligible	0.0656%	1,524
Admixed American	0.03%	3,334
African / African-American	0.0187%	5,352
Finnishnot grpmax-eligible	0.00468%	21,346

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: PEX2
Protein: p.Arg94Ser
Coding: c.282A>T
MANE Select: NM_000318
dbSNP: rs140963177
Type: single nucleotide variant
Location: chr8:76983897 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17
Residue 94: a UniProt-annotated variant site (in pbd5a)

Full PEX2 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: peroxisome biogenesis disorder 5A (Zellweger)peroxisome biogenesis disorder 5B Zellweger spectrum disorders

Similar variants

PEX2 p.Arg94Gly Uncertain significance ★ ⚠ same residue
PEX2 p.Arg94fs Pathogenic/Likely pathogenic ★★ same residue
PEX2 c.-17-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Arg119Ter Pathogenic ★★ same condition
PEX2 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Gln31Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Gln78Ter Pathogenic/Likely pathogenic ★★ same condition
PEX2 p.Gln96Ter 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/pex2-p-arg94ser (accessed [today's date]).

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