Is PEX1 p.Arg827Gln (c.2480G>A) pathogenic?

PEX1 p.Arg827Gln (c.2480G>A) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-10). AlphaMissense: likely benign (0.115); Ultra-rare (popmax 0.0164%, mid); Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Arg827Gln (c.2480G>A)?

PEX1 p.Arg827Gln (c.2480G>A) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Arg827Gln (c.2480G>A) in the general population?

PEX1 p.Arg827Gln (c.2480G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

How is Zellweger syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PEX1 p.Arg827Gln (c.2480G>A)?

AlphaMissense predicts likely benign (score 0.115) — an in-silico prediction, not a clinical call.

PEX1 p.Arg827Gln

c.2480G>A · rs752937649 · VCV2187028

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.115 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
AlphaMissense	0.115	likely benign
REVEL	0.686	pathogenic-leaning
SaProt	LLR -8.29	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.1, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	24.6	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000718%

Overall 0.0013% 21/1,613,744 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.00144%	69,400
South Asian	0.0011%	91,082

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: PEX1
Protein: p.Arg827Gln
Coding: c.2480G>A
MANE Select: NM_000466
dbSNP: rs752937649
Type: single nucleotide variant
Location: chr7:92501610 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 827: a UniProt-annotated variant site (in pbd1a)

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Zellweger spectrum disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Zellweger syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PEX1 p.Arg827Ter Pathogenic ★★ same residue
PEX1 p.Arg827Pro Uncertain significance ★ ⚠ same residue
PEX1 p.Arg827= Likely benign ★ same residue
PEX1 p.Arg827fs Pathogenic ★★ same residue
PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>T 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/pex1-p-arg827gln (accessed [today's date]).

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