Is PEX7 p.Phe24Leu (c.72C>A) pathogenic?

PEX7 p.Phe24Leu (c.72C>A) is classified Uncertain significance in PEX7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: likely pathogenic (0.9494); No allele count reported in gnomAD v4.1 (AN 1,499,124); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Phe24Leu (c.72C>A)?

PEX7 p.Phe24Leu (c.72C>A) is associated with peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Phe24Leu (c.72C>A) in the general population?

PEX7 p.Phe24Leu (c.72C>A) is no allele count reported in gnomAD v4.1 (AN 1,499,124) (gnomAD).

What do computational predictors say about PEX7 p.Phe24Leu (c.72C>A)?

AlphaMissense predicts likely pathogenic (score 0.9494) — an in-silico prediction, not a clinical call.

PEX7 p.Phe24Leu

c.72C>A · rs1774100078 · VCV2003648

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9494 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,499,124)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

peroxisome biogenesis disorder 9B

Computational evidence

Protein change
AlphaMissense	0.9494	likely pathogenic
REVEL	0.606	indeterminate
SaProt	LLR -10.66	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.75	GERP 1.6, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,499,124). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEX7
Protein: p.Phe24Leu
Coding: c.72C>A
MANE Select: NM_000288
dbSNP: rs1774100078
Type: single nucleotide variant
Location: chr6:136822737 (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.Phe24= Likely benign ★ same residue
PEX7 p.Phe24fs Pathogenic ★ 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

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-phe24leu (accessed [today's date]).

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