Is PEX3 p.Pro158Arg (c.473C>G) pathogenic?

PEX3 p.Pro158Arg (c.473C>G) is classified Conflicting classifications of pathogenicity in PEX3 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-28). AlphaMissense: likely benign (0.2879); Rare (popmax 0.21%, eas); Associated with peroxisome biogenesis disorder 10A (Zellweger).

What condition is associated with PEX3 p.Pro158Arg (c.473C>G)?

PEX3 p.Pro158Arg (c.473C>G) is associated with peroxisome biogenesis disorder 10A (Zellweger) (ClinVar).

How common is PEX3 p.Pro158Arg (c.473C>G) in the general population?

PEX3 p.Pro158Arg (c.473C>G) is rare (popmax 0.21%, eas) (gnomAD).

What do computational predictors say about PEX3 p.Pro158Arg (c.473C>G)?

AlphaMissense predicts likely benign (score 0.2879) — an in-silico prediction, not a clinical call.

PEX3 p.Pro158Arg

c.473C>G · rs199781957 · VCV291279

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2879 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.21%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 10A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.2879	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -9.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.21 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 1.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 38 kb · p 8.4e-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 0.21% East Asian · 94/44,736 alleles

Filtering AF 0.176% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.163%

Overall 0.0143% 230/1,606,602 alleles · rare exomes 207/1,454,320 · genomes 23/152,282 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.21%	476
Ashkenazi Jewishnot grpmax-eligible	0.166%	602
Remaining individualsnot grpmax-eligible	0.0257%	3,888
Middle Eastern	0.0165%	6,044
South Asian	0.00992%	10,082
European (non-Finnish)	0.00503%	19,891
Admixed American	0.00333%	30,010

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: PEX3
Protein: p.Pro158Arg
Coding: c.473C>G
MANE Select: NM_003630
dbSNP: rs199781957
Type: single nucleotide variant
Location: chr6:143471399 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 158: an α-helix

Full PEX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

peroxisome biogenesis disorder 10A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PEX3 p.Pro158Ala Uncertain significance ★ ⚠ same residue
PEX3 p.Pro158Ser Uncertain significance ★ ⚠ same residue
PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX3 c.-96G>T Uncertain significance ★★ same condition
PEX3 p.Arg300Gln Uncertain significance ★★ ⚠ same condition
PEX3 p.Asp305Glu Uncertain significance ★★ ⚠ same condition
PEX3 p.Glu266Asp Uncertain significance ★★ ⚠ same condition
PEX3 p.Met270Ile Uncertain significance ★★ ⚠ 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/pex3-p-pro158arg (accessed [today's date]).

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