Is PEX3 p.Val26Ile (c.76G>A) pathogenic?

PEX3 p.Val26Ile (c.76G>A) is classified Uncertain significance in PEX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-06). AlphaMissense: likely benign (0.0904); Absent from gnomAD v4.1.

How common is PEX3 p.Val26Ile (c.76G>A) in the general population?

PEX3 p.Val26Ile (c.76G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX3 p.Val26Ile (c.76G>A)?

AlphaMissense predicts likely benign (score 0.0904) — an in-silico prediction, not a clinical call.

PEX3 p.Val26Ile

c.76G>A · rs2537181976 · VCV2053750

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0904 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0904	likely benign
REVEL	0.064	moderately benign-leaning
SaProt	LLR -6.52	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.5	GERP 3.1, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 38 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	16.98	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PEX3
Protein: p.Val26Ile
Coding: c.76G>A
MANE Select: NM_003630
dbSNP: rs2537181976
Type: single nucleotide variant
Location: chr6:143459087 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 26: the 'targeting to peroxisomes' region

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

Similar variants

PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same type
PEX3 c.942-1G>T Likely pathogenic ★★ same type
PEX3 p.Arg256Ter Pathogenic/Likely pathogenic ★★ same type
PEX3 p.Arg286Ter Pathogenic ★★ same type
PEX3 p.Trp6Ter Pathogenic ★★ same type
PEX3 c.818+3A>G Uncertain significance ★★ same type
PEX3 c.-96G>T Uncertain significance ★★ same type
PEX3 p.Ala358Val Uncertain significance ★★ ⚠ 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-val26ile (accessed [today's date]).

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