Is PEX1 c.3207+2C>A pathogenic?

PEX1 c.3207+2C>A is classified Likely pathogenic in PEX1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-05-23). Very rare (popmax 0.0011%, sas); Associated with peroxisome biogenesis disorder 1A (Zellweger).

What condition is associated with PEX1 c.3207+2C>A?

PEX1 c.3207+2C>A is associated with peroxisome biogenesis disorder 1A (Zellweger) (ClinVar).

How common is PEX1 c.3207+2C>A in the general population?

PEX1 c.3207+2C>A is very rare (popmax 0.0011%, sas) (gnomAD).

PEX1 c.3207+2C>A

rs1554368097 · VCV558452

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

canonical splice-site (±1/±2)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Conditions

peroxisome biogenesis disorder 1A (Zellweger)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	canonical splice-site (±1/±2)	predicted loss-of-function
Splicing
Splice region	donor +2	canonical splice dinucleotide (donor +2) · inside the BP7-excluded zone
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.83	loss · gain 0.04 · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Non-coding constraint	Z 0.81	1 kb window · o/e 0.94 · regional · uncalibrated
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,980 alleles

Overall 0.000137% 2/1,457,688 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,980
European (non-Finnish)	8.5e-05%	1,176,251

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: PEX1
Coding: c.3207+2C>A
MANE Select: NM_021167 · reported on NM_000466
dbSNP: rs1554368097
Type: single nucleotide variant
Location: chr7:92492951 (GRCh38)

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 1A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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/pex1-c-3207-plus-2c-a (accessed [today's date]).

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