Is PEX7 p.Leu296Phe (c.886C>T) pathogenic?

PEX7 p.Leu296Phe (c.886C>T) is classified Uncertain significance in PEX7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-05-03). AlphaMissense: likely benign (0.2206); Very rare (popmax 0.00805%, afr); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Leu296Phe (c.886C>T)?

PEX7 p.Leu296Phe (c.886C>T) is associated with peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Leu296Phe (c.886C>T) in the general population?

PEX7 p.Leu296Phe (c.886C>T) is very rare (popmax 0.00805%, afr) (gnomAD).

What do computational predictors say about PEX7 p.Leu296Phe (c.886C>T)?

AlphaMissense predicts likely benign (score 0.2206) — an in-silico prediction, not a clinical call.

PEX7 p.Leu296Phe

c.886C>T · rs760967879 · VCV199007

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2206 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00805%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

peroxisome biogenesis disorder 9B

Computational evidence

Protein change
AlphaMissense	0.2206	likely benign
REVEL	0.482	indeterminate
SaProt	LLR -8.93	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 2.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	25.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00805% African / African-American · 6/74,562 alleles

Filtering AF 0.00348% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00239%

Overall 0.000376% 6/1,595,696 alleles · very rare exomes 0/1,443,522 · genomes 6/152,174 · 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.Leu296Phe
Coding: c.886C>T
MANE Select: NM_000288
dbSNP: rs760967879
Type: single nucleotide variant
Location: chr6:136898224 (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 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
PEX7 c.803+1G>A 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-leu296phe (accessed [today's date]).

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