Is PEX14 p.Pro295Ser (c.883C>T) pathogenic?

PEX14 p.Pro295Ser (c.883C>T) is classified Uncertain significance in PEX14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-28). AlphaMissense: likely benign (0.0666); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder, complementation group K.

How common is PEX14 p.Pro295Ser (c.883C>T) in the general population?

PEX14 p.Pro295Ser (c.883C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX14 p.Pro295Ser (c.883C>T)?

AlphaMissense predicts likely benign (score 0.0666) — an in-silico prediction, not a clinical call.

PEX14 p.Pro295Ser

Q: What condition is associated with PEX14 p.Pro295Ser (c.883C>T)?

PEX14 p.Pro295Ser (c.883C>T) is associated with peroxisome biogenesis disorder, complementation group K, peroxisome biogenesis disorder 13A (Zellweger) (ClinVar).

c.883C>T · rs886045017 · VCV291680

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0666 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder, complementation group K

Computational evidence

Protein change
AlphaMissense	0.0666	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -4.54	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 1.1	GERP -0.15, phastCons 0.5
Regional constraint	o/e 0.90	unconstrained · MANE · 325 bp · p 0.21 · regional, not allelic
Overall
CADD	15.72	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX14
Protein: p.Pro295Ser
Coding: c.883C>T
MANE Select: NM_004565
dbSNP: rs886045017
Type: single nucleotide variant
Location: chr1:10629736 (GRCh38)
Gene constraint: LOEUF 0.542 · pLI 0.91 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 68.48 · 4 PDB
Residue 295: the 'disordered' region

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

Also linked: peroxisome biogenesis disorder 13A (Zellweger)

Similar variants

PEX14 p.Pro295His Uncertain significance ★★ ⚠ same residue
PEX14 p.Pro295Thr Uncertain significance ★ ⚠ same residue
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

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-pro295ser (accessed [today's date]).

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