Is PRPS1 p.Pro170Ser (c.508C>T) pathogenic?

PRPS1 p.Pro170Ser (c.508C>T) is classified Uncertain significance in PRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-18). AlphaMissense: likely pathogenic (0.9979); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with PRPS1 p.Pro170Ser (c.508C>T)?

PRPS1 p.Pro170Ser (c.508C>T) is associated with Charcot-Marie-Tooth Neuropathy X (ClinVar).

How common is PRPS1 p.Pro170Ser (c.508C>T) in the general population?

PRPS1 p.Pro170Ser (c.508C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPS1 p.Pro170Ser (c.508C>T)?

AlphaMissense predicts likely pathogenic (score 0.9979) — an in-silico prediction, not a clinical call.

PRPS1 p.Pro170Ser

c.508C>T · rs1925595833 · VCV942389

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9979 · 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	0.9979	likely pathogenic
REVEL	0.924	moderately pathogenic-leaning
SaProt	LLR -14.98	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 17 kb · p 6.6e-28 · regional, not allelic
Overall
CADD	26.3	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.Pro170Ser
Coding: c.508C>T
MANE Select: NM_002764
dbSNP: rs1925595833
Type: single nucleotide variant
Location: chrX:107642468 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 170: 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-pro170ser (accessed [today's date]).

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