Is PEX7 p.Ala172Pro (c.514G>C) pathogenic?

PEX7 p.Ala172Pro (c.514G>C) is classified Uncertain significance in PEX7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-07-10). AlphaMissense: likely pathogenic (0.9886); Absent from gnomAD v4.1; Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Ala172Pro (c.514G>C)?

PEX7 p.Ala172Pro (c.514G>C) is associated with peroxisome biogenesis disorder 9B (ClinVar).

How common is PEX7 p.Ala172Pro (c.514G>C) in the general population?

PEX7 p.Ala172Pro (c.514G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX7 p.Ala172Pro (c.514G>C)?

AlphaMissense predicts likely pathogenic (score 0.9886) — an in-silico prediction, not a clinical call.

PEX7 p.Ala172Pro

c.514G>C · rs1562734989 · VCV594676

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9886 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 9B

Computational evidence

Protein change
AlphaMissense	0.9886	likely pathogenic · top 4% in PEX7
REVEL	0.892	moderately pathogenic-leaning
SaProt	LLR -16.38	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	32.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX7
Protein: p.Ala172Pro
Coding: c.514G>C
MANE Select: NM_000288
dbSNP: rs1562734989
Type: single nucleotide variant
Location: chr6:136846169 (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.Ala172= 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
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-ala172pro (accessed [today's date]).

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