Is PRPS1 p.Arg214Pro (c.641G>C) pathogenic?

PRPS1 p.Arg214Pro (c.641G>C) is classified Likely pathogenic in PRPS1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2017-01-01). AlphaMissense: likely pathogenic (0.9985); Absent from gnomAD v4.1; Associated with inherited retinal dystrophy.

What condition is associated with PRPS1 p.Arg214Pro (c.641G>C)?

PRPS1 p.Arg214Pro (c.641G>C) is associated with inherited retinal dystrophy (ClinVar).

How common is PRPS1 p.Arg214Pro (c.641G>C) in the general population?

PRPS1 p.Arg214Pro (c.641G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPS1 p.Arg214Pro (c.641G>C)?

AlphaMissense predicts likely pathogenic (score 0.9985) — an in-silico prediction, not a clinical call.

PRPS1 p.Arg214Pro

c.641G>C · rs867288458 · VCV446164

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9985 · 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	0.9985	likely pathogenic ✓ concordant with ClinVar
REVEL	0.754	pathogenic-leaning
SaProt	LLR -15.86	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 6.6	GERP 2.3, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 2,497 bp · p 1.3e-07 · regional, not allelic
Overall
CADD	25.3	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.Arg214Pro
Coding: c.641G>C
MANE Select: NM_002764
dbSNP: rs867288458
Type: single nucleotide variant
Location: chrX:107645287 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 214: the 'binding of phosphoribosylpyrophosphate' region; a β-strand

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.Arg214Trp Pathogenic/Likely pathogenic ★★ same residue
PRPS1 p.Arg214Gln Uncertain significance ★★ ⚠ same residue
PRPS1 p.Arg196Trp Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Asp128Val Conflicting classifications of pathogenicity ★ ⚠ same condition
PRPS1 p.Ser16Phe Likely pathogenic same condition
PRPS1 p.Arg84Trp Pathogenic/Likely pathogenic ★★ same type
PRPS1 p.Asn114Ser Likely pathogenic ★★ ⚠ same type
PRPS1 p.Ile107Val 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-arg214pro (accessed [today's date]).

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