Is PEX10 p.Arg281= (c.843G>A) pathogenic?

PEX10 p.Arg281= (c.843G>A) is classified Benign in PEX10 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Low-frequency (popmax 2.55%, afr); Associated with Peroxisome biogenesis disorder, complementation group 7.

What condition is associated with PEX10 p.Arg281= (c.843G>A)?

PEX10 p.Arg281= (c.843G>A) is associated with Peroxisome biogenesis disorder, complementation group 7, peroxisome biogenesis disorder 6A (Zellweger), Zellweger spectrum disorders (ClinVar).

How common is PEX10 p.Arg281= (c.843G>A) in the general population?

PEX10 p.Arg281= (c.843G>A) is low-frequency (popmax 2.55%, afr) (gnomAD).

PEX10 p.Arg281=

c.843G>A · rs35082957 · VCV262790

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.55%, afr)

Conditions

Peroxisome biogenesis disorder, complementation group 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.33	GERP -4.1, phastCons 0.94
Overall
CADD	5.025	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.55% African / African-American · 1,917/75,046 alleles

Filtering AF 2.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.42%

Overall 0.149% 2,411/1,613,310 alleles · low-frequency exomes 1,216/1,460,992 · genomes 1,195/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.55%	39
Admixed American	0.385%	260
Remaining individualsnot grpmax-eligible	0.243%	411
Middle Eastern	0.099%	1,010
European (non-Finnish)	0.00839%	11,919
South Asian	0.00659%	15,181

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: PEX10
Protein: p.Arg281=
Coding: c.843G>A
MANE Select: NM_002617
dbSNP: rs35082957
Type: single nucleotide variant
Location: chr1:2406553 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81
Residue 281: a UniProt-annotated variant site (in pbd6b and pbd6a)

Full PEX10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Peroxisome biogenesis disorder, complementation group 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 6A (Zellweger)Zellweger spectrum disorders

Similar variants

PEX10 p.Arg281Gly Uncertain significance ★ ⚠ same residue
PEX10 c.113-1G>A Likely pathogenic ★★ same condition
PEX10 c.600+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+1G>A Likely pathogenic ★★ same condition
PEX10 c.776+1G>C Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+2T>C Likely pathogenic ★★ same condition
PEX10 c.777-1G>A Likely pathogenic ★★ same condition
PEX10 c.912+1G>C Pathogenic/Likely 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/pex10-p-arg281 (accessed [today's date]).

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