Is PEX26 p.Pro148Ser (c.442C>T) pathogenic?

PEX26 p.Pro148Ser (c.442C>T) is classified Uncertain significance in PEX26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-10). AlphaMissense: likely benign (0.0907); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX26 p.Pro148Ser (c.442C>T)?

PEX26 p.Pro148Ser (c.442C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PEX26 p.Pro148Ser (c.442C>T) in the general population?

PEX26 p.Pro148Ser (c.442C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PEX26 p.Pro148Ser (c.442C>T)?

AlphaMissense predicts likely benign (score 0.0907) — an in-silico prediction, not a clinical call.

PEX26 p.Pro148Ser

c.442C>T · VCV3930958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0907 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0907	likely benign
REVEL	0.404	indeterminate
SaProt	LLR -7.57	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.29	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 0.86	GERP 0.92, phastCons 0.002
Regional constraint	o/e 0.98	unconstrained · MANE · 9,695 bp · p 0.72 · regional, not allelic
Overall
CADD	19.79	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,978 alleles

Overall 0.000137% 2/1,461,816 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,496
European (non-Finnish)grpmax	8.47e-05%	1,179,979

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PEX26
Protein: p.Pro148Ser
Coding: c.442C>T
MANE Select: NM_001127649
Type: single nucleotide variant
Location: chr22:18083507 (GRCh38)
Gene constraint: LOEUF 0.893 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.87

Full PEX26 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

Similar variants

PEX26 p.Pro148Thr Uncertain significance ★ ⚠ same residue
PEX26 p.Pro148= Likely benign ★ same residue
PEX26 p.Ala10Val Uncertain significance ★★ ⚠ same condition
PEX26 p.Ala143Thr Uncertain significance ★★ ⚠ same condition
PEX26 p.Ala202Val Uncertain significance ★★ ⚠ same condition
PEX26 p.Arg237His Uncertain significance ★★ ⚠ same condition
PEX26 p.Arg26His Uncertain significance ★★ ⚠ same condition
PEX26 p.Arg291Gln 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/pex26-p-pro148ser (accessed [today's date]).

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