Is PEX7 p.Pro26Ala (c.76C>G) pathogenic?

PEX7 p.Pro26Ala (c.76C>G) is classified Uncertain significance in PEX7 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-11). AlphaMissense: ambiguous (0.5565); Very rare (popmax 0.00146%, afr); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Pro26Ala (c.76C>G)?

PEX7 p.Pro26Ala (c.76C>G) is associated with peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Pro26Ala (c.76C>G) in the general population?

PEX7 p.Pro26Ala (c.76C>G) is very rare (popmax 0.00146%, afr) (gnomAD).

What do computational predictors say about PEX7 p.Pro26Ala (c.76C>G)?

AlphaMissense predicts ambiguous (score 0.5565) — an in-silico prediction, not a clinical call.

PEX7 p.Pro26Ala

c.76C>G · rs1774100244 · VCV2167795

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5565 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00146%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

peroxisome biogenesis disorder 9B

Computational evidence

Protein change
AlphaMissense	0.5565	ambiguous
REVEL	0.824	moderately pathogenic-leaning
SaProt	LLR -11.92	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.4	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00146% African / African-American · 1/68,684 alleles

Overall 6.68e-05% 1/1,496,678 alleles · very rare exomes 0/1,344,622 · genomes 1/152,056 · joint denominator

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.Pro26Ala
Coding: c.76C>G
MANE Select: NM_000288
dbSNP: rs1774100244
Type: single nucleotide variant
Location: chr6:136822741 (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.Pro26Leu Uncertain significance ★★ ⚠ same residue
PEX7 p.Pro26Arg Uncertain significance ★ ⚠ same residue
PEX7 p.Pro26= Likely benign ★ 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

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-pro26ala (accessed [today's date]).

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