Is PEX1 p.Val49= (c.147G>A) pathogenic?

PEX1 p.Val49= (c.147G>A) is classified Conflicting classifications of pathogenicity in PEX1 (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-01-05). Ultra-rare (popmax 0.066%, mid); Associated with peroxisome biogenesis disorder 1B.

What condition is associated with PEX1 p.Val49= (c.147G>A)?

PEX1 p.Val49= (c.147G>A) is associated with peroxisome biogenesis disorder 1B, peroxisome biogenesis disorder 1A (Zellweger), Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Val49= (c.147G>A) in the general population?

PEX1 p.Val49= (c.147G>A) is ultra-rare (popmax 0.066%, mid) (gnomAD).

PEX1 p.Val49=

c.147G>A · rs202230667 · VCV729928

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.066%, mid)

Conditions

peroxisome biogenesis disorder 1B

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 -0.86	GERP -4.5
Overall
CADD	1.827	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.066% Middle Eastern · 4/6,058 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0135%

Overall 0.00706% 114/1,614,052 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.066%	1,514
Remaining individualsnot grpmax-eligible	0.0272%	3,677
African / African-American	0.012%	8,338
South Asian	0.00769%	13,012
European (non-Finnish)	0.00627%	15,946
Admixed American	0.005%	20,006

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
Protein: p.Val49=
Coding: c.147G>A
MANE Select: NM_000466
dbSNP: rs202230667
Type: single nucleotide variant
Location: chr7:92522228 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19

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

Disease context

peroxisome biogenesis disorder 1B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 1A (Zellweger)Zellweger spectrum disorders

Similar variants

PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1483+1G>A Pathogenic ★★ same condition
PEX1 c.1587+1G>A Likely pathogenic ★★ same condition
PEX1 c.1670+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1670+1G>T 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/pex1-p-val49 (accessed [today's date]).

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