Is PEX2 p.Lys9Arg (c.26A>G) pathogenic?

PEX2 p.Lys9Arg (c.26A>G) is classified Uncertain significance in PEX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.0642); Very rare (popmax 0.000169%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX2 p.Lys9Arg (c.26A>G)?

PEX2 p.Lys9Arg (c.26A>G) is associated with Inborn genetic diseases (ClinVar).

How common is PEX2 p.Lys9Arg (c.26A>G) in the general population?

PEX2 p.Lys9Arg (c.26A>G) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about PEX2 p.Lys9Arg (c.26A>G)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

PEX2 p.Lys9Arg

c.26A>G · VCV4134909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.136	moderately benign-leaning
SaProt	LLR -6.16	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP 0.2
Regional constraint	o/e 0.99	unconstrained · MANE · 914 bp · p 0.85 · regional, not allelic
Overall
CADD	2.778	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

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,012 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,614,156 alleles · very rare exomes 2/1,461,836 · genomes 0/152,320 · joint denominator

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.Lys9Arg
Coding: c.26A>G
MANE Select: NM_000318
Type: single nucleotide variant
Location: chr8:76984153 (GRCh38)
Gene constraint: LOEUF 1.057 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.17

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

Similar variants

PEX2 p.Ala8Val Uncertain significance ★★ ⚠ same condition
PEX2 p.Arg125Gln Uncertain significance ★★ ⚠ same condition
PEX2 p.Arg51His Uncertain significance ★★ ⚠ same condition
PEX2 p.Asn7His Uncertain significance ★★ ⚠ same condition
PEX2 p.Cys184Tyr Uncertain significance ★★ ⚠ same condition
PEX2 p.Gln102Lys Uncertain significance ★★ ⚠ same condition
PEX2 p.Gln39Arg Uncertain significance ★★ ⚠ same condition
PEX2 p.Gly161Glu Uncertain significance ★★ ⚠ 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-lys9arg (accessed [today's date]).

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