Is PEX14 p.Asp377= (c.1131C>T) pathogenic?

PEX14 p.Asp377= (c.1131C>T) is classified Likely benign in PEX14 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-24). Ultra-rare (popmax 0.0208%, mid); Associated with peroxisome biogenesis disorder, complementation group K.

What condition is associated with PEX14 p.Asp377= (c.1131C>T)?

PEX14 p.Asp377= (c.1131C>T) is associated with peroxisome biogenesis disorder, complementation group K (ClinVar).

How common is PEX14 p.Asp377= (c.1131C>T) in the general population?

PEX14 p.Asp377= (c.1131C>T) is ultra-rare (popmax 0.0208%, mid) (gnomAD).

PEX14 p.Asp377=

c.1131C>T · rs2124651209 · VCV1590739

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0208%, mid)

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 4.6	GERP 2.1, phastCons 1
Overall
CADD	9.953	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0208% Middle Eastern · 1/4,802 alleles

Overall 0.000186% 3/1,609,152 alleles · ultra-rare exomes 3/1,458,226 · genomes 0/150,926 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0208%	4,802
South Asian	0.0011%	90,884
European (non-Finnish)	8.48e-05%	1,179,536

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.Asp377=
Coding: c.1131C>T
MANE Select: NM_004565
dbSNP: rs2124651209
Type: single nucleotide variant
Location: chr1:10629984 (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 377: 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 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-asp377 (accessed [today's date]).

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