Is PEX14 p.Val256= (c.768G>A) pathogenic?

PEX14 p.Val256= (c.768G>A) is classified Benign/Likely benign in PEX14 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-02-04). Low-frequency (popmax 1.78%, nfe); Associated with peroxisome biogenesis disorder 13A (Zellweger).

What condition is associated with PEX14 p.Val256= (c.768G>A)?

PEX14 p.Val256= (c.768G>A) is associated with peroxisome biogenesis disorder 13A (Zellweger), peroxisome biogenesis disorder, complementation group K (ClinVar).

How common is PEX14 p.Val256= (c.768G>A) in the general population?

PEX14 p.Val256= (c.768G>A) is low-frequency (popmax 1.78%, nfe) (gnomAD).

PEX14 p.Val256=

c.768G>A · rs36083022 · VCV259437

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.78%, nfe)

Conditions

peroxisome biogenesis disorder 13A (Zellweger)

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 1.8	GERP -2.8, phastCons 0.95
Overall
CADD	2.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.78% European (non-Finnish) · 20,957/1,179,826 alleles

Filtering AF 1.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.75%

Overall 1.44% 23,271/1,613,660 alleles · low-frequency exomes 21,698/1,461,660 · genomes 1,573/152,000 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.78%	56
Amishnot grpmax-eligible	1.21%	83
Remaining individualsnot grpmax-eligible	1.1%	91
Middle Eastern	0.924%	108
Admixed American	0.64%	156
Ashkenazi Jewishnot grpmax-eligible	0.557%	179
South Asian	0.524%	191
Finnishnot grpmax-eligible	0.505%	198
African / African-American	0.275%	364
East Asian	0.00446%	22,418

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.Val256=
Coding: c.768G>A
MANE Select: NM_004565
dbSNP: rs36083022
Type: single nucleotide variant
Location: chr1:10629621 (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 256: the 'disordered' region

Full PEX14 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 13A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder, complementation group K

Similar variants

PEX14 p.Val256Ala Uncertain significance ★ ⚠ same residue
PEX14 p.Val256Met Conflicting classifications of pathogenicity ★ ⚠ 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-val256 (accessed [today's date]).

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