Is PEX10 p.Arg244Pro (c.731G>C) pathogenic?

PEX10 p.Arg244Pro (c.731G>C) is classified Uncertain significance in PEX10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-09). AlphaMissense: ambiguous (0.3916); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX10 p.Arg244Pro (c.731G>C)?

PEX10 p.Arg244Pro (c.731G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PEX10 p.Arg244Pro (c.731G>C) in the general population?

PEX10 p.Arg244Pro (c.731G>C) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about PEX10 p.Arg244Pro (c.731G>C)?

AlphaMissense predicts ambiguous (score 0.3916) — an in-silico prediction, not a clinical call.

PEX10 p.Arg244Pro

c.731G>C · rs149877113 · VCV594956

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.3916 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3916	ambiguous
REVEL	0.619	indeterminate
SaProt	LLR -16.40	damaging
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.3	GERP 0.99, phastCons 0.7
Regional constraint	o/e 1.06	unconstrained · MANE · 6,733 bp · p 0.24 · 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 0.00017% European (non-Finnish) · 2/1,178,592 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,609,230 alleles · very rare exomes 0/1,456,990 · genomes 2/152,240 · joint denominator

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: PEX10
Protein: p.Arg244Pro
Coding: c.731G>C
MANE Select: NM_002617
dbSNP: rs149877113
Type: single nucleotide variant
Location: chr1:2406765 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.81
Residue 244: a UniProt-annotated variant site (in pbd6b and pbd6a)

Full PEX10 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

Similar variants

PEX10 p.Arg244Ter Pathogenic ★★ same residue
PEX10 p.Arg244Gln Uncertain significance ★★ ⚠ same residue
PEX10 c.776+1G>C Pathogenic/Likely pathogenic ★★ same condition
PEX10 p.Ala159Pro Uncertain significance ★★ ⚠ same condition
PEX10 p.Ala305Val Uncertain significance ★★ ⚠ same condition
PEX10 p.Arg143His Uncertain significance ★★ ⚠ same condition
PEX10 p.Arg146Cys Uncertain significance ★★ ⚠ same condition
PEX10 p.Arg157Lys Uncertain significance ★★ ⚠ 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/pex10-p-arg244pro (accessed [today's date]).

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