Is PRPS1 p.Val289fs (c.864_865insCC) pathogenic?

PRPS1 p.Val289fs (c.864865insCC) is classified Uncertain significance in PRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-18). Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with PRPS1 p.Val289fs (c.864_865insCC)?

PRPS1 p.Val289fs (c.864_865insCC) is associated with Charcot-Marie-Tooth Neuropathy X (ClinVar).

PRPS1 p.Val289fs

c.864_865insCC · VCV4731498

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

Charcot-Marie-Tooth Neuropathy X

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: PRPS1
Protein: p.Val289fs
Coding: c.864_865insCC
MANE Select: NM_002764
Type: Insertion
Location: chrX:107649939 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 289: 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.Val289= Likely benign ★ same residue
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

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-val289fs (accessed [today's date]).

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