Is PRPS1 p.Asp98Val (c.293A>T) pathogenic?

PRPS1 p.Asp98Val (c.293A>T) is classified Uncertain significance in PRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-22). AlphaMissense: likely pathogenic (0.9996); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with PRPS1 p.Asp98Val (c.293A>T)?

PRPS1 p.Asp98Val (c.293A>T) is associated with Charcot-Marie-Tooth Neuropathy X (ClinVar).

How common is PRPS1 p.Asp98Val (c.293A>T) in the general population?

PRPS1 p.Asp98Val (c.293A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPS1 p.Asp98Val (c.293A>T)?

AlphaMissense predicts likely pathogenic (score 0.9996) — an in-silico prediction, not a clinical call.

PRPS1 p.Asp98Val

c.293A>T · VCV3639151

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9996 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth Neuropathy X

Computational evidence

Protein change
AlphaMissense	0.9996	likely pathogenic · top 4% in PRPS1
REVEL	0.91	moderately pathogenic-leaning
SaProt	LLR -15.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.74 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.1	GERP 2.2, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 17 kb · p 6.6e-28 · regional, not allelic
Overall
CADD	29.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PRPS1
Protein: p.Asp98Val
Coding: c.293A>T
MANE Select: NM_002764
Type: single nucleotide variant
Location: chrX:107639465 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 98: a binding site

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.Asp98Asn Uncertain significance ★★ ⚠ 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-asp98val (accessed [today's date]).

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