Is PEX3 p.Arg300Pro (c.899G>C) pathogenic?

PEX3 p.Arg300Pro (c.899G>C) is classified Uncertain significance in PEX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-24). AlphaMissense: likely pathogenic (0.627); Very rare (popmax 0.0011%, sas).

How common is PEX3 p.Arg300Pro (c.899G>C) in the general population?

PEX3 p.Arg300Pro (c.899G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about PEX3 p.Arg300Pro (c.899G>C)?

AlphaMissense predicts likely pathogenic (score 0.627) — an in-silico prediction, not a clinical call.

PEX3 p.Arg300Pro

c.899G>C · rs200463608 · VCV1443265

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.627	likely pathogenic
REVEL	0.198	benign-leaning
SaProt	LLR -6.42	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.33	donor loss · deltas
Constraint at this position
Conservation	phyloP 8.5	GERP 2, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 38 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	26.4	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 0.0011% South Asian · 1/90,846 alleles

Overall 0.000125% 2/1,604,580 alleles · very rare exomes 2/1,452,566 · genomes 0/152,014 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	90,846
European (non-Finnish)	8.53e-05%	1,171,742

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: PEX3
Protein: p.Arg300Pro
Coding: c.899G>C
MANE Select: NM_003630
dbSNP: rs200463608
Type: single nucleotide variant
Location: chr6:143479156 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB

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

Similar variants

PEX3 p.Arg300Gln Uncertain significance ★★ ⚠ same residue
PEX3 p.Arg300Ter Pathogenic 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-arg300pro (accessed [today's date]).

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