Is PEX14 p.Phe52= (c.156C>T) pathogenic?

PEX14 p.Phe52= (c.156C>T) is classified Benign in PEX14 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-04). Common (popmax 38.6%, amr) — too common for a highly-penetrant pathogenic allele; Associated with peroxisome biogenesis disorder, complementation group K.

What condition is associated with PEX14 p.Phe52= (c.156C>T)?

PEX14 p.Phe52= (c.156C>T) is associated with peroxisome biogenesis disorder, complementation group K, peroxisome biogenesis disorder 13A (Zellweger) (ClinVar).

PEX14 p.Phe52=

Q: How common is PEX14 p.Phe52= (c.156C>T) in the general population?

PEX14 p.Phe52= (c.156C>T) is common (popmax 38.6%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.156C>T · rs12375 · VCV259434

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 38.6%, amr) — too common for a highly-penetrant pathogenic allele

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 2.1	GERP 1, phastCons 1
Overall
CADD	13.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 38.6% Admixed American · 23,179/59,982 alleles

Filtering AF 38.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 38.1%

Overall 30.5% 487,013/1,596,574 alleles · common exomes 447,902/1,444,612 · genomes 39,111/151,962 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	38.6%	3
Amishnot grpmax-eligible	35.1%	3
Finnishnot grpmax-eligible	33.3%	3
European (non-Finnish)	32.5%	3
Remaining individualsnot grpmax-eligible	29.6%	3
Ashkenazi Jewishnot grpmax-eligible	26.6%	4
Middle Eastern	22.8%	4
South Asian	22.3%	4
East Asian	18.9%	5
African / African-American	10.3%	10

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.Phe52=
Coding: c.156C>T
MANE Select: NM_004565
dbSNP: rs12375
Type: single nucleotide variant
Location: chr1:10536284 (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 52: an α-helix

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.Phe52Leu 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
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-phe52 (accessed [today's date]).

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