Is PEX10 p.Arg323Pro (c.968G>C) pathogenic?

PEX10 p.Arg323Pro (c.968G>C) is classified Uncertain significance in PEX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-11). AlphaMissense: likely pathogenic (0.7988); Very rare (popmax 0.0034%, amr); Associated with Peroxisome biogenesis disorder, complementation group 7.

What condition is associated with PEX10 p.Arg323Pro (c.968G>C)?

PEX10 p.Arg323Pro (c.968G>C) is associated with Peroxisome biogenesis disorder, complementation group 7 (ClinVar).

How common is PEX10 p.Arg323Pro (c.968G>C) in the general population?

PEX10 p.Arg323Pro (c.968G>C) is very rare (popmax 0.0034%, amr) (gnomAD).

What do computational predictors say about PEX10 p.Arg323Pro (c.968G>C)?

AlphaMissense predicts likely pathogenic (score 0.7988) — an in-silico prediction, not a clinical call.

PEX10 p.Arg323Pro

c.968G>C · rs781194710 · VCV2202598

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7988 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0034%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Peroxisome biogenesis disorder, complementation group 7

Computational evidence

Protein change
AlphaMissense	0.7988	likely pathogenic
REVEL	0.605	indeterminate
SaProt	LLR -9.11	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP 2.1, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 6,733 bp · p 0.24 · regional, not allelic
Overall
CADD	28.4	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 0.0034% Admixed American · 2/58,884 alleles

Filtering AF 0.000563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000187% 3/1,603,332 alleles · very rare exomes 3/1,450,978 · genomes 0/152,354 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0034%	29,442
European (non-Finnish)	8.51e-05%	1,175,326

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.Arg323Pro
Coding: c.968G>C
MANE Select: NM_002617
dbSNP: rs781194710
Type: single nucleotide variant
Location: chr1:2405779 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81
Residue 323: 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

Similar variants

PEX10 p.Arg323Trp Uncertain significance ★★ ⚠ same residue
PEX10 c.113-1G>A Likely pathogenic ★★ same condition
PEX10 c.776+1G>A Likely pathogenic ★★ same condition
PEX10 p.Arg125Ter Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Met1Ile Pathogenic/Likely pathogenic ★★ same condition
PEX10 c.776+5G>A Uncertain significance ★★ same condition
PEX10 p.Ala150Val Uncertain significance ★★ ⚠ same condition
PEX10 p.Ala163Val 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/pex10-p-arg323pro (accessed [today's date]).

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