Is PEX14 p.Ser265= (c.795A>G) pathogenic?

PEX14 p.Ser265= (c.795A>G) is classified Conflicting classifications of pathogenicity in PEX14 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-04). Rare (popmax 0.859%, nfe); Associated with peroxisome biogenesis disorder, complementation group K.

What condition is associated with PEX14 p.Ser265= (c.795A>G)?

PEX14 p.Ser265= (c.795A>G) is associated with peroxisome biogenesis disorder, complementation group K, peroxisome biogenesis disorder 13A (Zellweger) (ClinVar).

How common is PEX14 p.Ser265= (c.795A>G) in the general population?

PEX14 p.Ser265= (c.795A>G) is rare (popmax 0.859%, nfe) (gnomAD).

PEX14 p.Ser265=

c.795A>G · rs41274484 · VCV286053

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.859%, nfe)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.7	GERP -4.3
Overall
CADD	0.333	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.859% European (non-Finnish) · 9,967/1,159,942 alleles

Filtering AF 0.845% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.839%

Overall 0.675% 10,730/1,590,558 alleles · rare exomes 10,068/1,440,604 · genomes 662/149,954 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.859%	116
Remaining individualsnot grpmax-eligible	0.51%	196
Admixed American	0.236%	424
Ashkenazi Jewishnot grpmax-eligible	0.197%	507
African / African-American	0.125%	803
South Asian	0.114%	879
Finnishnot grpmax-eligible	0.0817%	1,224
Middle Eastern	0.0333%	3,007

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.Ser265=
Coding: c.795A>G
MANE Select: NM_004565
dbSNP: rs41274484
Type: single nucleotide variant
Location: chr1:10629648 (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 265: 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 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-ser265 (accessed [today's date]).

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