Is PEX26 p.Ala30Val (c.89C>T) pathogenic?

PEX26 p.Ala30Val (c.89C>T) is classified Uncertain significance in PEX26 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-06). AlphaMissense: likely benign (0.0987); Very rare (popmax 0.00043%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX26 p.Ala30Val (c.89C>T)?

PEX26 p.Ala30Val (c.89C>T) is associated with Inborn genetic diseases (ClinVar).

How common is PEX26 p.Ala30Val (c.89C>T) in the general population?

PEX26 p.Ala30Val (c.89C>T) is very rare (popmax 0.00043%, nfe) (gnomAD).

What do computational predictors say about PEX26 p.Ala30Val (c.89C>T)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

PEX26 p.Ala30Val

c.89C>T · VCV3930959

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00043%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -6.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.48	GERP 3.5
Regional constraint	o/e 0.98	unconstrained · MANE · 9,695 bp · p 0.72 · regional, not allelic
Overall
CADD	16.69	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 0.00043% European (non-Finnish) · 5/1,163,630 alleles

Filtering AF 0.000126% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.2e-05%

Overall 0.000351% 5/1,424,164 alleles · very rare

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.Ala30Val
Coding: c.89C>T
MANE Select: NM_001127649
Type: single nucleotide variant
Location: chr22:18078465 (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.Ala30= 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
PEX26 p.Arg297His 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-ala30val (accessed [today's date]).

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