Is PEX7 p.Glu80= (c.240A>G) pathogenic?

PEX7 p.Glu80= (c.240A>G) is classified Likely benign in PEX7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). Very rare (popmax 0.005%, amr); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Glu80= (c.240A>G)?

PEX7 p.Glu80= (c.240A>G) is associated with peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Glu80= (c.240A>G) in the general population?

PEX7 p.Glu80= (c.240A>G) is very rare (popmax 0.005%, amr) (gnomAD).

PEX7 p.Glu80=

c.240A>G · rs777854575 · VCV1134602

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 9B

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.28	GERP -0.65, phastCons 0.55
Overall
CADD	5.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,988 alleles

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

Overall 0.00031% 5/1,613,996 alleles · very rare exomes 5/1,461,850 · genomes 0/152,146 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,996
European (non-Finnish)	0.000169%	589,995

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: PEX7
Protein: p.Glu80=
Coding: c.240A>G
MANE Select: NM_000288
dbSNP: rs777854575
Type: single nucleotide variant
Location: chr6:136826370 (GRCh38)
Gene constraint: LOEUF 0.941 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.54

Full PEX7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 9B — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX7 p.Glu80Lys Uncertain significance ★★ ⚠ same residue
PEX7 c.130+1G>A Pathogenic ★★ same condition
PEX7 c.131-1G>A Likely pathogenic ★★ same condition
PEX7 c.188+1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.188+1G>C Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.340-1G>T Likely pathogenic ★★ same condition
PEX7 c.634-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX7 c.748-2A>G Likely 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/pex7-p-glu80 (accessed [today's date]).

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