Is PEX10 p.Pro121= (c.363C>T) pathogenic?

PEX10 p.Pro121= (c.363C>T) is classified Conflicting classifications of pathogenicity in PEX10 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-01-13). Very rare (popmax 0.004%, afr); Associated with Peroxisome biogenesis disorder, complementation group 7.

What condition is associated with PEX10 p.Pro121= (c.363C>T)?

PEX10 p.Pro121= (c.363C>T) is associated with Peroxisome biogenesis disorder, complementation group 7 (ClinVar).

How common is PEX10 p.Pro121= (c.363C>T) in the general population?

PEX10 p.Pro121= (c.363C>T) is very rare (popmax 0.004%, afr) (gnomAD).

PEX10 p.Pro121=

c.363C>T · rs543982780 · VCV595575

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, 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 -5	GERP -3.5
Overall
CADD	0.765	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/75,032 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00118% 19/1,613,042 alleles · very rare exomes 14/1,460,746 · genomes 5/152,296 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	25,011
East Asian	0.00223%	44,850
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.00119%	84,261

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.Pro121=
Coding: c.363C>T
MANE Select: NM_002617
dbSNP: rs543982780
Type: single nucleotide variant
Location: chr1:2408689 (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.Pro121Ser Uncertain significance ★ ⚠ same residue
PEX10 p.Pro121Thr 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

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-pro121 (accessed [today's date]).

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