Is PEX1 p.Ala611Val (c.1832C>T) pathogenic?

PEX1 p.Ala611Val (c.1832C>T) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 2 submitters; last evaluated 2021-09-24). AlphaMissense: likely pathogenic (0.6465); Absent from gnomAD v4.1; Associated with Zellweger spectrum disorders.

What condition is associated with PEX1 p.Ala611Val (c.1832C>T)?

PEX1 p.Ala611Val (c.1832C>T) is associated with Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Ala611Val (c.1832C>T) in the general population?

PEX1 p.Ala611Val (c.1832C>T) is absent from gnomAD v4.1 (gnomAD).

How is Zellweger syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PEX1 p.Ala611Val (c.1832C>T)?

AlphaMissense predicts likely pathogenic (score 0.6465) — an in-silico prediction, not a clinical call.

PEX1 p.Ala611Val

c.1832C>T · rs2116176413 · VCV1351456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6465 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Zellweger spectrum disorders

Computational evidence

Protein change
AlphaMissense	0.6465	likely pathogenic
REVEL	0.628	indeterminate
SaProt	LLR -11.79	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.20	loss · gain 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 12	GERP 3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	27.0	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: PEX1
Protein: p.Ala611Val
Coding: c.1832C>T
MANE Select: NM_000466
dbSNP: rs2116176413
Type: single nucleotide variant
Location: chr7:92506316 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Zellweger spectrum disorders — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Zellweger syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

PEX1 p.Ala611= Likely benign ★ same residue
PEX1 p.Ala611fs Likely pathogenic ★ same residue
PEX1 c.1239+1G>T Pathogenic ★★ same condition
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same condition
PEX1 c.1483+1G>A Pathogenic ★★ same condition
PEX1 c.1587+1G>A Likely pathogenic ★★ 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/pex1-p-ala611val (accessed [today's date]).

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