Is PEX3 p.Phe18= (c.54C>T) pathogenic?

PEX3 p.Phe18= (c.54C>T) is classified Likely benign in PEX3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-12-28). Ultra-rare (popmax 0.0165%, mid); Associated with PEX3-related disorder.

What condition is associated with PEX3 p.Phe18= (c.54C>T)?

PEX3 p.Phe18= (c.54C>T) is associated with PEX3-related disorder (ClinVar).

How common is PEX3 p.Phe18= (c.54C>T) in the general population?

PEX3 p.Phe18= (c.54C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

PEX3 p.Phe18=

c.54C>T · rs1408332322 · VCV3036528

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

PEX3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.7	GERP 2.4, phastCons 1
Overall
CADD	15.53	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000248% 4/1,613,290 alleles · ultra-rare exomes 4/1,461,072 · genomes 0/152,218 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
South Asian	0.00329%	30,357

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.Phe18=
Coding: c.54C>T
MANE Select: NM_003630
dbSNP: rs1408332322
Type: single nucleotide variant
Location: chr6:143451096 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 18: the 'targeting to peroxisomes' region

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

Disease context

PEX3-related disorder

Similar variants

PEX3 c.942-1G>T Likely pathogenic ★★ same condition
PEX3 p.Arg256Ter Pathogenic/Likely pathogenic ★★ same condition
PEX3 c.579-1G>A Likely pathogenic ★ same condition
PEX3 p.Gly331Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
PEX3 p.Ser273Asn Uncertain significance ⚠ same condition
PEX3 p.Met81fs Likely pathogenic ★ same condition
PEX3 p.Pro158fs Likely pathogenic ★ same condition
PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same type

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-phe18 (accessed [today's date]).

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