Is PEX14 p.Pro98= (c.294A>G) pathogenic?

PEX14 p.Pro98= (c.294A>G) is classified Likely benign in PEX14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-27). Very rare (popmax 0.00167%, amr); Associated with peroxisome biogenesis disorder, complementation group K.

What condition is associated with PEX14 p.Pro98= (c.294A>G)?

PEX14 p.Pro98= (c.294A>G) is associated with peroxisome biogenesis disorder, complementation group K (ClinVar).

How common is PEX14 p.Pro98= (c.294A>G) in the general population?

PEX14 p.Pro98= (c.294A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

PEX14 p.Pro98=

c.294A>G · rs1459322335 · VCV1667310

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00167%, 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 -2.1	GERP -5.1
Overall
CADD	4.225	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,004 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000372% 6/1,614,064 alleles · very rare exomes 5/1,461,868 · genomes 1/152,196 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	74,928
European (non-Finnish)	0.000254%	393,340

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.Pro98=
Coding: c.294A>G
MANE Select: NM_004565
dbSNP: rs1459322335
Type: single nucleotide variant
Location: chr1:10599362 (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-pro98 (accessed [today's date]).

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