Is PEX3 p.Val131Phe (c.391G>T) pathogenic?

PEX3 p.Val131Phe (c.391G>T) is classified Uncertain significance in PEX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-03). AlphaMissense: likely pathogenic (0.8996); Absent from gnomAD v4.1.

How common is PEX3 p.Val131Phe (c.391G>T) in the general population?

PEX3 p.Val131Phe (c.391G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX3 p.Val131Phe (c.391G>T)?

AlphaMissense predicts likely pathogenic (score 0.8996) — an in-silico prediction, not a clinical call.

PEX3 p.Val131Phe

c.391G>T · rs2537196792 · VCV1715047

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8996	likely pathogenic
REVEL	0.649	pathogenic-leaning
SaProt	LLR -12.16	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 38 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	28.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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.Val131Phe
Coding: c.391G>T
MANE Select: NM_003630
dbSNP: rs2537196792
Type: single nucleotide variant
Location: chr6:143471020 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 131: an α-helix; the 'interaction with pex19' region

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

Similar variants

PEX3 p.Val131Ala Uncertain significance ★ ⚠ same residue
PEX3 p.Val131= Likely benign ★ same residue
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

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-val131phe (accessed [today's date]).

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