Is PEX14 p.Pro45Ser (c.133C>T) pathogenic?

PEX14 p.Pro45Ser (c.133C>T) is classified Uncertain significance in PEX14 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.3362); Very rare (popmax 0.00034%, nfe); Associated with peroxisome biogenesis disorder, complementation group K.

What condition is associated with PEX14 p.Pro45Ser (c.133C>T)?

PEX14 p.Pro45Ser (c.133C>T) is associated with peroxisome biogenesis disorder, complementation group K (ClinVar).

How common is PEX14 p.Pro45Ser (c.133C>T) in the general population?

PEX14 p.Pro45Ser (c.133C>T) is very rare (popmax 0.00034%, nfe) (gnomAD).

What do computational predictors say about PEX14 p.Pro45Ser (c.133C>T)?

AlphaMissense predicts likely benign (score 0.3362) — an in-silico prediction, not a clinical call.

PEX14 p.Pro45Ser

c.133C>T · rs1374474122 · VCV2157279

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3362 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00034%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

peroxisome biogenesis disorder, complementation group K

Computational evidence

Protein change
AlphaMissense	0.3362	likely benign
REVEL	0.467	indeterminate
SaProt	LLR -8.64	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 2.2, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 93 kb · p 2.3e-08 · regional, not allelic
Overall
CADD	27.7	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 0.00034% European (non-Finnish) · 4/1,177,632 alleles

Filtering AF 8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,611,442 alleles · very rare exomes 4/1,459,268 · genomes 0/152,174 · joint denominator

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: PEX14
Protein: p.Pro45Ser
Coding: c.133C>T
MANE Select: NM_004565
dbSNP: rs1374474122
Type: single nucleotide variant
Location: chr1:10536261 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.91 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 4 PDB

Full PEX14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder, complementation group K — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX14 c.36+6G>T Uncertain significance ★★ same condition
PEX14 p.Ala102Thr Uncertain significance ★★ ⚠ same condition
PEX14 p.Ala254Val Uncertain significance ★★ ⚠ same condition
PEX14 p.Ala370Ser Uncertain significance ★★ ⚠ same condition
PEX14 p.Arg105Gln Uncertain significance ★★ ⚠ same condition
PEX14 p.Arg139Leu Uncertain significance ★★ ⚠ same condition
PEX14 p.Arg142Lys Uncertain significance ★★ ⚠ same condition
PEX14 p.Arg350Cys 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/pex14-p-pro45ser (accessed [today's date]).

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