Is PEX1 p.Arg183Gln (c.548G>A) pathogenic?

PEX1 p.Arg183Gln (c.548G>A) is classified Conflicting classifications of pathogenicity in PEX1 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2022-06-19). AlphaMissense: likely benign (0.0533); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with PEX1 p.Arg183Gln (c.548G>A)?

PEX1 p.Arg183Gln (c.548G>A) is associated with Inborn genetic diseases, Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Arg183Gln (c.548G>A) in the general population?

PEX1 p.Arg183Gln (c.548G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about PEX1 p.Arg183Gln (c.548G>A)?

AlphaMissense predicts likely benign (score 0.0533) — an in-silico prediction, not a clinical call.

PEX1 p.Arg183Gln

c.548G>A · rs371413721 · VCV2159278

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0533 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0533	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -5.04	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 2.9	GERP -0.36, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	11.31	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 0.0165% Middle Eastern · 1/6,048 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000822% 12/1,459,126 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,048
Remaining individualsnot grpmax-eligible	0.00321%	31,185
African / African-American	0.00134%	74,860
South Asian	0.0011%	90,628
European (non-Finnish)	0.000594%	168,415

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.Arg183Gln
Coding: c.548G>A
MANE Select: NM_000466
dbSNP: rs371413721
Type: single nucleotide variant
Location: chr7:92517967 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Zellweger spectrum disorders

Similar variants

PEX1 p.Arg183Ter Pathogenic/Likely pathogenic ★★ same residue
PEX1 p.Arg183Gly Uncertain significance ★ ⚠ 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
PEX1 c.1483+1G>A Pathogenic ★★ same condition
PEX1 c.1587+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/pex1-p-arg183gln (accessed [today's date]).

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