Is PRPS1 p.Ile4= (c.12C>T) pathogenic?

PRPS1 p.Ile4= (c.12C>T) is classified Benign/Likely benign in PRPS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-06-09). Very rare (popmax 0.000558%, nfe); Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with PRPS1 p.Ile4= (c.12C>T)?

PRPS1 p.Ile4= (c.12C>T) is associated with Charcot-Marie-Tooth Neuropathy X (ClinVar).

How common is PRPS1 p.Ile4= (c.12C>T) in the general population?

PRPS1 p.Ile4= (c.12C>T) is very rare (popmax 0.000558%, nfe) (gnomAD).

PRPS1 p.Ile4=

c.12C>T · rs752590804 · VCV666743

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000558%, nfe)

Conditions

Charcot-Marie-Tooth Neuropathy X

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.16	GERP -3, phastCons 0.43
Overall
CADD	12.89	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000558% European (non-Finnish) · 5/895,270 alleles

Filtering AF 0.000164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000119%

Overall 0.000413% 5/1,209,882 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: PRPS1
Protein: p.Ile4=
Coding: c.12C>T
MANE Select: NM_002764
dbSNP: rs752590804
Type: single nucleotide variant
Location: chrX:107628640 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 4: a β-strand

Full PRPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Charcot-Marie-Tooth Neuropathy X — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPS1 p.Ile107Val Likely pathogenic ★★ same condition
PRPS1 p.Met115Thr Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Ser169Leu Pathogenic ★★ same condition
PRPS1 p.Ala216Thr Uncertain significance ★★ ⚠ same condition
PRPS1 p.Arg204Cys Uncertain significance ★★ ⚠ same condition
PRPS1 p.Arg204His Uncertain significance ★★ same condition
PRPS1 p.Arg260Cys Uncertain significance ★★ ⚠ same condition
PRPS1 p.Arg260His 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/prps1-p-ile4 (accessed [today's date]).

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