Is PEX14 p.Arg351Pro (c.1052G>C) pathogenic?

PEX14 p.Arg351Pro (c.1052G>C) is classified Uncertain significance in PEX14 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-07). AlphaMissense: likely pathogenic (0.7049); Very rare (popmax 0.000254%, nfe); Associated with peroxisome biogenesis disorder, complementation group K.

What condition is associated with PEX14 p.Arg351Pro (c.1052G>C)?

PEX14 p.Arg351Pro (c.1052G>C) is associated with peroxisome biogenesis disorder, complementation group K (ClinVar).

How common is PEX14 p.Arg351Pro (c.1052G>C) in the general population?

PEX14 p.Arg351Pro (c.1052G>C) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about PEX14 p.Arg351Pro (c.1052G>C)?

AlphaMissense predicts likely pathogenic (score 0.7049) — an in-silico prediction, not a clinical call.

PEX14 p.Arg351Pro

c.1052G>C · rs960056444 · VCV2048122

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7049 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

peroxisome biogenesis disorder, complementation group K

Computational evidence

Protein change
AlphaMissense	0.7049	likely pathogenic
REVEL	0.362	indeterminate
SaProt	LLR -6.94	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 2.1, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 325 bp · p 0.21 · regional, not allelic
Overall
CADD	24.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,848 alleles

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

Overall 0.000186% 3/1,613,482 alleles · very rare exomes 3/1,461,502 · genomes 0/151,980 · joint denominator

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.Arg351Pro
Coding: c.1052G>C
MANE Select: NM_004565
dbSNP: rs960056444
Type: single nucleotide variant
Location: chr1:10629905 (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 351: 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.Arg351Gln Uncertain significance ★ ⚠ same residue
PEX14 p.Arg351Trp 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-arg351pro (accessed [today's date]).

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