Is PEX10 p.Pro8Ser (c.22C>T) pathogenic?

PEX10 p.Pro8Ser (c.22C>T) is classified Uncertain significance in PEX10 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-27). AlphaMissense: likely benign (0.136); Very rare (popmax 0.00454%, afr); Associated with Peroxisome biogenesis disorder, complementation group 7.

What condition is associated with PEX10 p.Pro8Ser (c.22C>T)?

PEX10 p.Pro8Ser (c.22C>T) is associated with Peroxisome biogenesis disorder, complementation group 7 (ClinVar).

How common is PEX10 p.Pro8Ser (c.22C>T) in the general population?

PEX10 p.Pro8Ser (c.22C>T) is very rare (popmax 0.00454%, afr) (gnomAD).

What do computational predictors say about PEX10 p.Pro8Ser (c.22C>T)?

AlphaMissense predicts likely benign (score 0.136) — an in-silico prediction, not a clinical call.

PEX10 p.Pro8Ser

c.22C>T · rs781306925 · VCV2081368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.136 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00454%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Peroxisome biogenesis disorder, complementation group 7

Computational evidence

Protein change
AlphaMissense	0.136	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -8.03	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 0.84	GERP -4, phastCons 0.22
Regional constraint	o/e 1.06	unconstrained · MANE · 6,733 bp · p 0.24 · regional, not allelic
Overall
CADD	16.3	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 0.00454% African / African-American · 3/66,140 alleles

Filtering AF 0.0012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000634%

Overall 0.00144% 20/1,384,160 alleles · very rare exomes 14/1,232,106 · genomes 6/152,054 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0352%	2,841
Remaining individualsnot grpmax-eligible	0.00762%	13,122
African / African-Americangrpmax	0.00454%	22,047
South Asian	0.00161%	62,100
European (non-Finnish)	0.000373%	267,928

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro8Ser
Coding: c.22C>T
MANE Select: NM_002617
dbSNP: rs781306925
Type: single nucleotide variant
Location: chr1:2412481 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81

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.Pro8His Uncertain significance ★ ⚠ same residue
PEX10 p.Pro8= Likely benign ★ same residue
PEX10 p.Pro8Thr 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

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-pro8ser (accessed [today's date]).

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