Is SPR p.Pro89Arg (c.266C>G) pathogenic?

SPR p.Pro89Arg (c.266C>G) is classified Uncertain significance in SPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). AlphaMissense: likely benign (0.26); Absent from gnomAD v4.1; Associated with dystonic disorder.

What condition is associated with SPR p.Pro89Arg (c.266C>G)?

SPR p.Pro89Arg (c.266C>G) is associated with dystonic disorder (ClinVar).

How common is SPR p.Pro89Arg (c.266C>G) in the general population?

SPR p.Pro89Arg (c.266C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SPR p.Pro89Arg (c.266C>G)?

AlphaMissense predicts likely benign (score 0.26) — an in-silico prediction, not a clinical call.

SPR p.Pro89Arg

c.266C>G · VCV3627635

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.26 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.26	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -13.44	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.7	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 4,101 bp · p 0.27 · regional, not allelic
Overall
CADD	19.66	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: SPR
Protein: p.Pro89Arg
Coding: c.266C>G
MANE Select: NM_003124
Type: single nucleotide variant
Location: chr2:72887698 (GRCh38)
Gene constraint: LOEUF 1.528 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.71 · 14 PDB
Residue 89: an α-helix

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

Disease context

dystonic disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPR p.Pro89Leu Uncertain significance ★★ ⚠ same residue
SPR p.Arg150Gly Pathogenic ★★ same condition
SPR p.Arg219Ter Pathogenic ★★ same condition
SPR p.Cys171Tyr Likely pathogenic ★★ same condition
SPR p.Gln182Ter Pathogenic ★★ same condition
SPR p.Gln239Ter Pathogenic ★★ same condition
SPR p.Lys230Ter Pathogenic/Likely pathogenic ★★ same condition
SPR p.Lys251Ter Pathogenic ★★ 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/spr-p-pro89arg (accessed [today's date]).

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