Is PEX7 p.Arg232Gln (c.695G>A) pathogenic?

PEX7 p.Arg232Gln (c.695G>A) is classified Conflicting classifications of pathogenicity in PEX7 (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2025-12-29). AlphaMissense: likely benign (0.0758); Rare (popmax 0.453%, eas); Associated with peroxisome biogenesis disorder 9B.

What condition is associated with PEX7 p.Arg232Gln (c.695G>A)?

PEX7 p.Arg232Gln (c.695G>A) is associated with peroxisome biogenesis disorder 9B, rhizomelic chondrodysplasia punctata type 1, adult Refsum disease (ClinVar).

How common is PEX7 p.Arg232Gln (c.695G>A) in the general population?

PEX7 p.Arg232Gln (c.695G>A) is rare (popmax 0.453%, eas) (gnomAD).

What do computational predictors say about PEX7 p.Arg232Gln (c.695G>A)?

AlphaMissense predicts likely benign (score 0.0758) — an in-silico prediction, not a clinical call.

PEX7 p.Arg232Gln

c.695G>A · rs191969418 · VCV500853

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0758 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.453%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 9B

Computational evidence

Protein change
AlphaMissense	0.0758	likely benign
REVEL	0.073	moderately benign-leaning
SaProt	LLR -6.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 91 kb · p 0.75 · regional, not allelic
Overall
CADD	21.2	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 0.453% East Asian · 203/44,858 alleles

Filtering AF 0.402% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.382%

Overall 0.0159% 256/1,614,020 alleles · rare exomes 225/1,461,746 · genomes 31/152,274 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.453%	221
Remaining individualsnot grpmax-eligible	0.0176%	5,683
South Asian	0.0165%	6,072
European (non-Finnish)	0.00212%	47,197
Admixed American	0.00167%	60,016
Finnishnot grpmax-eligible	0.00156%	64,014

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.Arg232Gln
Coding: c.695G>A
MANE Select: NM_000288
dbSNP: rs191969418
Type: single nucleotide variant
Location: chr6:136869951 (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

Also linked: rhizomelic chondrodysplasia punctata type 1 adult Refsum disease

Similar variants

PEX7 p.Arg232Ter 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
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-arg232gln (accessed [today's date]).

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