Is PEX5 p.Ser565= (c.1695C>T) pathogenic?

PEX5 p.Ser565= (c.1695C>T) is classified Likely benign in PEX5 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-22). Very rare (popmax 0.00246%, nfe); Associated with peroxisome biogenesis disorder 2B.

What condition is associated with PEX5 p.Ser565= (c.1695C>T)?

PEX5 p.Ser565= (c.1695C>T) is associated with peroxisome biogenesis disorder 2B (ClinVar).

How common is PEX5 p.Ser565= (c.1695C>T) in the general population?

PEX5 p.Ser565= (c.1695C>T) is very rare (popmax 0.00246%, nfe) (gnomAD).

PEX5 p.Ser565=

c.1695C>T · rs755547376 · VCV745728

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Conditions

peroxisome biogenesis disorder 2B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.8	GERP 1.8, phastCons 1
Overall
CADD	12.44	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,180,044 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00192% 31/1,614,102 alleles · very rare exomes 25/1,461,886 · genomes 6/152,216 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,691
East Asian	0.00223%	44,900
African / African-American	0.00133%	74,928

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: PEX5
Protein: p.Ser565=
Coding: c.1695C>T
MANE Select: NM_001351132
dbSNP: rs755547376
Type: single nucleotide variant
Location: chr12:7209817 (GRCh38)
Gene constraint: LOEUF 0.768 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.28 · 11 PDB
Residue 565: a UniProt-annotated variant site (in pbd2b; impaired ability to mediate peroxisomal import of proteins containing both a c-terminal pts1- and pts2-type targeting signals); an α-helix

Full PEX5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 2B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX5 c.449-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.552-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX5 c.847-2A>G Likely pathogenic ★★ same condition
PEX5 c.967-1G>A Likely pathogenic ★★ same condition
PEX5 p.Arg237Ter Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Arg276Ter Pathogenic/Likely pathogenic ★★ same condition
PEX5 p.Arg420Ter Pathogenic ★★ same condition
PEX5 p.Arg427Ter 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/pex5-p-ser565 (accessed [today's date]).

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