Is PEX3 p.Ile109Val (c.325A>G) pathogenic?

PEX3 p.Ile109Val (c.325A>G) is classified Uncertain significance in PEX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-01). AlphaMissense: likely benign (0.1046); No allele count reported in gnomAD v4.1 (AN 1,587,638).

How common is PEX3 p.Ile109Val (c.325A>G) in the general population?

PEX3 p.Ile109Val (c.325A>G) is no allele count reported in gnomAD v4.1 (AN 1,587,638) (gnomAD).

What do computational predictors say about PEX3 p.Ile109Val (c.325A>G)?

AlphaMissense predicts likely benign (score 0.1046) — an in-silico prediction, not a clinical call.

PEX3 p.Ile109Val

c.325A>G · rs2537193182 · VCV2068086

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1046 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,587,638)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1046	likely benign
REVEL	0.15	moderately benign-leaning
SaProt	LLR -5.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.50	donor gain · deltas
Pangolin	Δ0.54	gain · loss 0.37 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 38 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	26.2	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

No allele count reported in gnomAD v4.1 (AN 1,587,638). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PEX3
Protein: p.Ile109Val
Coding: c.325A>G
MANE Select: NM_003630
dbSNP: rs2537193182
Type: single nucleotide variant
Location: chr6:143468159 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 109: an α-helix

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-ile109val (accessed [today's date]).

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