Is PEX1 p.Arg1275Pro (c.3824G>C) pathogenic?

PEX1 p.Arg1275Pro (c.3824G>C) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: ambiguous (0.3738); Very rare (popmax 0.0045%, eas).

How common is PEX1 p.Arg1275Pro (c.3824G>C) in the general population?

PEX1 p.Arg1275Pro (c.3824G>C) is very rare (popmax 0.0045%, eas) (gnomAD).

What do computational predictors say about PEX1 p.Arg1275Pro (c.3824G>C)?

AlphaMissense predicts ambiguous (score 0.3738) — an in-silico prediction, not a clinical call.

PEX1 p.Arg1275Pro

c.3824G>C · VCV4541305

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3738 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0045%, eas)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3738	ambiguous
REVEL	0.736	pathogenic-leaning
SaProt	LLR -6.17	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.6	GERP 3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	25.0	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 0.0045% East Asian · 2/44,458 alleles

Filtering AF 0.000746% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000279%

Overall 0.000125% 2/1,593,732 alleles · very rare

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.Arg1275Pro
Coding: c.3824G>C
MANE Select: NM_021167 · reported on NM_000466
Type: single nucleotide variant
Location: chr7:92487485 (GRCh38)

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

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-arg1275pro (accessed [today's date]).

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