Is PRPS1 p.Ser16Phe (c.47C>T) pathogenic?

PRPS1 p.Ser16Phe (c.47C>T) is classified Likely pathogenic in PRPS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-01-01). AlphaMissense: likely pathogenic (0.9652); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with PRPS1 p.Ser16Phe (c.47C>T)?

PRPS1 p.Ser16Phe (c.47C>T) is associated with inherited retinal dystrophy (ClinVar).

How common is PRPS1 p.Ser16Phe (c.47C>T) in the general population?

PRPS1 p.Ser16Phe (c.47C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPS1 p.Ser16Phe (c.47C>T)?

AlphaMissense predicts likely pathogenic (score 0.9652) — an in-silico prediction, not a clinical call.

PRPS1 p.Ser16Phe

c.47C>T · rs1556297584 · VCV446161

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9652 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

inherited retinal dystrophy

Computational evidence

Protein change
AlphaMissense	0.9652	likely pathogenic ✓ concordant with ClinVar
REVEL	0.882	moderately pathogenic-leaning
SaProt	LLR -17.57	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 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 17 kb · p 6.6e-28 · regional, not allelic
Overall
CADD	28.0	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.Ser16Phe
Coding: c.47C>T
MANE Select: NM_002764
dbSNP: rs1556297584
Type: single nucleotide variant
Location: chrX:107628675 (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

inherited retinal dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PRPS1 p.Ser16Pro Pathogenic same residue
PRPS1 p.Arg196Trp Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Arg214Trp Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Arg214Gln Uncertain significance ★★ ⚠ same condition
PRPS1 p.Asp128Val Conflicting classifications of pathogenicity ★ ⚠ same condition
PRPS1 p.Arg214Pro Likely pathogenic same condition
PRPS1 p.Arg84Trp Pathogenic/Likely pathogenic ★★ same type
PRPS1 p.Asn114Ser Likely pathogenic ★★ ⚠ same type

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-ser16phe (accessed [today's date]).

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