Is PEX13 p.Ser80Phe (c.239C>T) pathogenic?

PEX13 p.Ser80Phe (c.239C>T) is classified Uncertain significance in PEX13 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.2173); Very rare (popmax 0.000169%, nfe); Associated with peroxisome biogenesis disorder 11A (Zellweger).

What condition is associated with PEX13 p.Ser80Phe (c.239C>T)?

PEX13 p.Ser80Phe (c.239C>T) is associated with peroxisome biogenesis disorder 11A (Zellweger) (ClinVar).

How common is PEX13 p.Ser80Phe (c.239C>T) in the general population?

PEX13 p.Ser80Phe (c.239C>T) is very rare (popmax 0.000169%, nfe) (gnomAD).

What do computational predictors say about PEX13 p.Ser80Phe (c.239C>T)?

AlphaMissense predicts likely benign (score 0.2173) — an in-silico prediction, not a clinical call.

PEX13 p.Ser80Phe

c.239C>T · rs2467507620 · VCV1715921

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2173 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

peroxisome biogenesis disorder 11A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.2173	likely benign
REVEL	0.544	indeterminate
SaProt	LLR -11.07	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 31 kb · p 0.0078 · regional, not allelic
Overall
CADD	26.4	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 0.000169% European (non-Finnish) · 2/1,180,020 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,461,878 alleles · very rare

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: PEX13
Protein: p.Ser80Phe
Coding: c.239C>T
MANE Select: NM_002618
dbSNP: rs2467507620
Type: single nucleotide variant
Location: chr2:61031565 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.62 · 3 PDB

Full PEX13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 11A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX13 p.Arg16Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 p.Arg226Ter Pathogenic ★★ same condition
PEX13 p.Gln131Ter Pathogenic ★★ same condition
PEX13 p.Glu123Ter Pathogenic ★★ same condition
PEX13 p.Tyr155Ter Pathogenic/Likely pathogenic ★★ same condition
PEX13 c.913+3A>G Uncertain significance ★★ same condition
PEX13 p.Ala302Gly 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/pex13-p-ser80phe (accessed [today's date]).

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