Is PRPS1 p.Ser254= (c.762C>T) pathogenic?

PRPS1 p.Ser254= (c.762C>T) is classified Likely benign in PRPS1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-12). Very rare (popmax 0.00218%, amr); Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with PRPS1 p.Ser254= (c.762C>T)?

PRPS1 p.Ser254= (c.762C>T) is associated with Charcot-Marie-Tooth Neuropathy X (ClinVar).

How common is PRPS1 p.Ser254= (c.762C>T) in the general population?

PRPS1 p.Ser254= (c.762C>T) is very rare (popmax 0.00218%, amr) (gnomAD).

PRPS1 p.Ser254=

c.762C>T · rs780750403 · VCV1153338

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00218%, amr)

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	<0.2	all four deltas below 0.2 · C>A here scores Δ0.39 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.17	GERP -4.5, phastCons 0.99
Overall
CADD	7.262	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00218% Admixed American · 1/45,957 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000413% 5/1,210,845 alleles · very rare exomes 5/1,097,658 · genomes 0/113,187 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00218%	45,957
Remaining individualsnot grpmax-eligible	0.0021%	47,618
South Asian	0.00176%	56,943
European (non-Finnish)	0.000223%	447,495

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.Ser254=
Coding: c.762C>T
MANE Select: NM_002764
dbSNP: rs780750403
Type: single nucleotide variant
Location: chrX:107647663 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 254: a turn

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-ser254 (accessed [today's date]).

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