Is PEX14 p.Pro248= (c.744G>A) pathogenic?

PEX14 p.Pro248= (c.744G>A) is classified Likely benign in PEX14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-20). Very rare (popmax 0.00401%, afr); Associated with peroxisome biogenesis disorder, complementation group K.

What condition is associated with PEX14 p.Pro248= (c.744G>A)?

PEX14 p.Pro248= (c.744G>A) is associated with peroxisome biogenesis disorder, complementation group K (ClinVar).

How common is PEX14 p.Pro248= (c.744G>A) in the general population?

PEX14 p.Pro248= (c.744G>A) is very rare (popmax 0.00401%, afr) (gnomAD).

PEX14 p.Pro248=

c.744G>A · rs145103775 · VCV1650844

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

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	GERP -4.3
Overall
CADD	1.084	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,896 alleles

Filtering AF 0.0018% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00156%

Overall 0.00229% 37/1,613,862 alleles · very rare exomes 33/1,461,726 · genomes 4/152,136 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,965
Remaining individualsnot grpmax-eligible	0.0032%	31,240
European (non-Finnish)	0.00254%	39,334
East Asian	0.00223%	44,892
Finnishnot grpmax-eligible	0.00156%	63,902

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.Pro248=
Coding: c.744G>A
MANE Select: NM_004565
dbSNP: rs145103775
Type: single nucleotide variant
Location: chr1:10629597 (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 248: 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

Similar variants

PEX14 p.Pro248Gln Uncertain significance ★★ ⚠ same residue
PEX14 p.Pro248Leu 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-pro248 (accessed [today's date]).

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