Is PEX1 p.Arg1127Trp (c.3379C>T) pathogenic?

PEX1 p.Arg1127Trp (c.3379C>T) is classified Uncertain significance in PEX1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-15). AlphaMissense: likely pathogenic (0.6825); Very rare (popmax 0.00271%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX1 p.Arg1127Trp (c.3379C>T)?

PEX1 p.Arg1127Trp (c.3379C>T) is associated with Inborn genetic diseases, Zellweger spectrum disorders (ClinVar).

How common is PEX1 p.Arg1127Trp (c.3379C>T) in the general population?

PEX1 p.Arg1127Trp (c.3379C>T) is very rare (popmax 0.00271%, nfe) (gnomAD).

What do computational predictors say about PEX1 p.Arg1127Trp (c.3379C>T)?

AlphaMissense predicts likely pathogenic (score 0.6825) — an in-silico prediction, not a clinical call.

PEX1 p.Arg1127Trp

c.3379C>T · rs769066970 · VCV2202226

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6825 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00271%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6825	likely pathogenic
REVEL	0.875	moderately pathogenic-leaning
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 10	GERP 3.9, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00271% European (non-Finnish) · 32/1,179,848 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00304% 49/1,613,702 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0032%	31,238
European (non-Finnish)grpmax	0.00271%	36,870
Admixed American	0.00167%	59,982
South Asian	0.0011%	91,080

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: PEX1
Protein: p.Arg1127Trp
Coding: c.3379C>T
MANE Select: NM_021167 · reported on NM_000466
dbSNP: rs769066970
Type: single nucleotide variant
Location: chr7:92491331 (GRCh38)

Full PEX1 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

Also linked: Zellweger spectrum disorders

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-arg1127trp (accessed [today's date]).

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