Is PRPS1 p.Ser16Pro (c.46T>C) pathogenic?

PRPS1 p.Ser16Pro (c.46T>C) is classified Pathogenic in PRPS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-09-23). AlphaMissense: likely pathogenic (0.9166); Absent from gnomAD v4.1; Associated with Charcot-Marie-Tooth disease X-linked recessive 5.

What condition is associated with PRPS1 p.Ser16Pro (c.46T>C)?

PRPS1 p.Ser16Pro (c.46T>C) is associated with Charcot-Marie-Tooth disease X-linked recessive 5 (ClinVar).

How common is PRPS1 p.Ser16Pro (c.46T>C) in the general population?

PRPS1 p.Ser16Pro (c.46T>C) is absent from gnomAD v4.1 (gnomAD).

How is X-linked Charcot-Marie-Tooth disease type 5 inherited?

Typically X-linked recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about PRPS1 p.Ser16Pro (c.46T>C)?

AlphaMissense predicts likely pathogenic (score 0.9166) — an in-silico prediction, not a clinical call.

PRPS1 p.Ser16Pro

c.46T>C · rs869025594 · VCV223101

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9166 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Charcot-Marie-Tooth disease X-linked recessive 5

Computational evidence

Protein change
AlphaMissense	0.9166	likely pathogenic ✓ concordant with ClinVar
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -14.45	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 6.1	GERP 2.3, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 17 kb · p 6.6e-28 · regional, not allelic
Overall
CADD	24.5	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

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.Ser16Pro
Coding: c.46T>C
MANE Select: NM_002764
dbSNP: rs869025594
Type: single nucleotide variant
Location: chrX:107628674 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 16: a UniProt-annotated variant site (found in patients with phosphoribosyl pyrophosphate synthetase i deficiency; likely pathogenic); an α-helix

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

Disease context

Charcot-Marie-Tooth disease X-linked recessive 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked Charcot-Marie-Tooth disease type 5 (Orphanet):

Inheritance: X-linked recessive
Onset: Childhood, Infancy
Prevalence: <1 / 1 000 000 (Worldwide)

Similar variants

PRPS1 p.Ser16Phe Likely pathogenic same residue
PRPS1 p.Ile107Val Likely pathogenic ★★ same condition
PRPS1 p.Met115Thr Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Met115Val Pathogenic/Likely pathogenic ★★ same condition
PRPS1 c.306+5G>T Uncertain significance ★★ same condition
PRPS1 p.Arg204His Uncertain significance ★★ same condition
PRPS1 p.Arg214Gln Uncertain significance ★★ ⚠ same condition
PRPS1 p.Val112Ile 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-ser16pro (accessed [today's date]).

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