Is PEX14 p.Ser158= (c.474C>T) pathogenic?

PEX14 p.Ser158= (c.474C>T) is classified Conflicting classifications of pathogenicity in PEX14 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-27). Very rare (popmax 0.00834%, amr); Associated with peroxisome biogenesis disorder, complementation group K.

What condition is associated with PEX14 p.Ser158= (c.474C>T)?

PEX14 p.Ser158= (c.474C>T) is associated with peroxisome biogenesis disorder, complementation group K (ClinVar).

How common is PEX14 p.Ser158= (c.474C>T) in the general population?

PEX14 p.Ser158= (c.474C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

PEX14 p.Ser158=

c.474C>T · rs145867351 · VCV285256

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Conditions

peroxisome biogenesis disorder, complementation group K

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 -0.2	GERP -4.1, phastCons 0.27
Overall
CADD	9.611	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00834% Admixed American · 5/59,964 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00093% 15/1,612,404 alleles · very rare exomes 14/1,460,292 · genomes 1/152,112 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,993
Remaining individualsnot grpmax-eligible	0.00641%	15,604
African / African-American	0.00267%	37,433
European (non-Finnish)	0.000339%	294,709

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.Ser158=
Coding: c.474C>T
MANE Select: NM_004565
dbSNP: rs145867351
Type: single nucleotide variant
Location: chr1:10623108 (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 p.Ser158Arg Conflicting classifications of pathogenicity ★ ⚠ 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
PEX14 p.Arg142Lys 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-ser158 (accessed [today's date]).

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