Is PRPS1 p.Ser83Ile (c.248G>T) pathogenic?

PRPS1 p.Ser83Ile (c.248G>T) is classified Uncertain significance in PRPS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-17). AlphaMissense: ambiguous (0.3821); Very rare (popmax 0.00349%, afr); Associated with Charcot-Marie-Tooth Neuropathy X.

What condition is associated with PRPS1 p.Ser83Ile (c.248G>T)?

PRPS1 p.Ser83Ile (c.248G>T) is associated with Charcot-Marie-Tooth Neuropathy X (ClinVar).

How common is PRPS1 p.Ser83Ile (c.248G>T) in the general population?

PRPS1 p.Ser83Ile (c.248G>T) is very rare (popmax 0.00349%, afr) (gnomAD).

What do computational predictors say about PRPS1 p.Ser83Ile (c.248G>T)?

AlphaMissense predicts ambiguous (score 0.3821) — an in-silico prediction, not a clinical call.

PRPS1 p.Ser83Ile

c.248G>T · rs767243595 · VCV3015392

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3821 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00349%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Charcot-Marie-Tooth Neuropathy X

Computational evidence

Protein change
AlphaMissense	0.3821	ambiguous
REVEL	0.695	pathogenic-leaning
SaProt	LLR -9.83	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 17 kb · p 6.6e-28 · 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

Grpmax group 0.00349% African / African-American · 2/57,231 alleles

Filtering AF 0.00058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000165% 2/1,210,054 alleles · very rare exomes 0/1,098,208 · genomes 2/111,846 · 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.Ser83Ile
Coding: c.248G>T
MANE Select: NM_002764
dbSNP: rs767243595
Type: single nucleotide variant
Location: chrX:107639420 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 83: a β-strand

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.Ser83Cys Uncertain significance ★★ ⚠ same residue
PRPS1 p.Ser83= Likely benign ★ same residue
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

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-ser83ile (accessed [today's date]).

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