Is PRPS1 p.Glu148= (c.444G>A) pathogenic?

PRPS1 p.Glu148= (c.444G>A) is classified Benign/Likely benign in PRPS1 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-09-06). Rare (popmax 0.16%, eas); Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with PRPS1 p.Glu148= (c.444G>A)?

PRPS1 p.Glu148= (c.444G>A) is associated with Charcot-Marie-Tooth Neuropathy X, phosphoribosylpyrophosphate synthetase superactivity, Arts syndrome (ClinVar).

How common is PRPS1 p.Glu148= (c.444G>A) in the general population?

PRPS1 p.Glu148= (c.444G>A) is rare (popmax 0.16%, eas) (gnomAD).

PRPS1 p.Glu148=

c.444G>A · rs201285459 · VCV367702

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.16%, eas)

Conditions

Charcot-Marie-Tooth Neuropathy X

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 0.24, phastCons 1
Overall
CADD	7.423	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.16% East Asian · 54/33,785 alleles

Filtering AF 0.126% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.114%

Overall 0.00446% 54/1,210,210 alleles · rare exomes 49/1,097,993 · genomes 5/112,217 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: PRPS1
Protein: p.Glu148=
Coding: c.444G>A
MANE Select: NM_002764
dbSNP: rs201285459
Type: single nucleotide variant
Location: chrX:107642404 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 148: an α-helix

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

Also linked: phosphoribosylpyrophosphate synthetase superactivity Arts syndrome hearing loss, X-linked 1

Similar variants

PRPS1 p.Arg214Trp Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Asn114Ser Likely pathogenic ★★ ⚠ same condition
PRPS1 p.Ile107Val Likely pathogenic ★★ same condition
PRPS1 p.Met115Thr Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Met115Val Pathogenic/Likely pathogenic ★★ same condition
PRPS1 p.Ser169Leu Pathogenic ★★ same condition
PRPS1 c.306+5G>T Uncertain significance ★★ same condition
PRPS1 c.*389G>A 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-glu148 (accessed [today's date]).

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