Is SPR p.Pro87Arg (c.260C>G) pathogenic?

SPR p.Pro87Arg (c.260C>G) is classified Uncertain significance in SPR (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-11). AlphaMissense: likely benign (0.1773); Very rare (popmax 0.00211%, amr); Associated with dystonic disorder.

What condition is associated with SPR p.Pro87Arg (c.260C>G)?

SPR p.Pro87Arg (c.260C>G) is associated with dystonic disorder (ClinVar).

How common is SPR p.Pro87Arg (c.260C>G) in the general population?

SPR p.Pro87Arg (c.260C>G) is very rare (popmax 0.00211%, amr) (gnomAD).

What do computational predictors say about SPR p.Pro87Arg (c.260C>G)?

AlphaMissense predicts likely benign (score 0.1773) — an in-silico prediction, not a clinical call.

SPR p.Pro87Arg

c.260C>G · rs1573881909 · VCV1438587

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00211%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

dystonic disorder

Computational evidence

Protein change
AlphaMissense	0.1773	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -9.65	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 4,101 bp · p 0.27 · regional, not allelic
Overall
CADD	16.96	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00211% Admixed American · 1/47,284 alleles

Overall 6.65e-05% 1/1,503,548 alleles · very rare exomes 0/1,351,198 · genomes 1/152,350 · 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: SPR
Protein: p.Pro87Arg
Coding: c.260C>G
MANE Select: NM_003124
dbSNP: rs1573881909
Type: single nucleotide variant
Location: chr2:72887692 (GRCh38)
Gene constraint: LOEUF 1.528 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.71 · 14 PDB
Residue 87: 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.Pro87Thr Uncertain significance ★ ⚠ same residue
SPR p.Pro87= Likely benign ★ 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

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-pro87arg (accessed [today's date]).

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