Is PRPS1 p.Ile74Val (c.220A>G) pathogenic?

PRPS1 p.Ile74Val (c.220A>G) is classified Uncertain significance in PRPS1 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-08-01). AlphaMissense: likely benign (0.1799); Absent from gnomAD v4.1.

How common is PRPS1 p.Ile74Val (c.220A>G) in the general population?

PRPS1 p.Ile74Val (c.220A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PRPS1 p.Ile74Val (c.220A>G)?

AlphaMissense predicts likely benign (score 0.1799) — an in-silico prediction, not a clinical call.

PRPS1 p.Ile74Val

c.220A>G · rs2147681457 · VCV1304820

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1799 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1799	likely benign
REVEL	0.647	pathogenic-leaning
SaProt	LLR -9.67	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.12	constrained · MANE · 17 kb · p 6.6e-28 · regional, not allelic
Overall
CADD	25.5	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.Ile74Val
Coding: c.220A>G
MANE Select: NM_002764
dbSNP: rs2147681457
Type: single nucleotide variant
Location: chrX:107639392 (GRCh38)
Structure: AlphaFold pLDDT 94.77 · 27 PDB
Residue 74: an α-helix

Full PRPS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PRPS1 p.Arg196Trp Pathogenic/Likely pathogenic ★★ same type
PRPS1 p.Arg214Trp Pathogenic/Likely pathogenic ★★ same type
PRPS1 p.Arg84Trp Pathogenic/Likely pathogenic ★★ same type
PRPS1 p.Asn114Ser Likely pathogenic ★★ ⚠ same type
PRPS1 p.Ile107Val Likely pathogenic ★★ same type
PRPS1 p.Met115Thr Pathogenic/Likely pathogenic ★★ same type
PRPS1 p.Met115Val Pathogenic/Likely pathogenic ★★ same type
PRPS1 p.Ser169Leu 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-ile74val (accessed [today's date]).

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