Is PEX12 p.Lys115= (c.345A>G) pathogenic?

PEX12 p.Lys115= (c.345A>G) is classified Likely benign in PEX12 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-27). Very rare (popmax 0.005%, amr); Associated with peroxisome biogenesis disorder 3A (Zellweger).

What condition is associated with PEX12 p.Lys115= (c.345A>G)?

PEX12 p.Lys115= (c.345A>G) is associated with peroxisome biogenesis disorder 3A (Zellweger) (ClinVar).

How common is PEX12 p.Lys115= (c.345A>G) in the general population?

PEX12 p.Lys115= (c.345A>G) is very rare (popmax 0.005%, amr) (gnomAD).

PEX12 p.Lys115=

c.345A>G · rs1293631647 · VCV1585076

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

peroxisome biogenesis disorder 3A (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 -0.73	phastCons 0.019
Overall
CADD	5.914	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/60,022 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,614,140 alleles · very rare exomes 4/1,461,846 · genomes 0/152,294 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,007
European (non-Finnish)	8.47e-05%	1,179,997

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: PEX12
Protein: p.Lys115=
Coding: c.345A>G
MANE Select: NM_000286
dbSNP: rs1293631647
Type: single nucleotide variant
Location: chr17:35577373 (GRCh38)
Gene constraint: LOEUF 1.218 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.58

Full PEX12 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 3A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX12 c.126+1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX12 c.680+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Arg154Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Arg180Ter Pathogenic ★★ same condition
PEX12 p.Arg202Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Gln111Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Gln112Ter Pathogenic/Likely pathogenic ★★ same condition
PEX12 p.Gln209Ter Pathogenic ★★ 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/pex12-p-lys115 (accessed [today's date]).

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