Is SPR p.Pro143= (c.429G>T) pathogenic?

SPR p.Pro143= (c.429G>T) is classified Likely benign in SPR (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). Very rare (popmax 0.000678%, nfe); Associated with dystonic disorder.

What condition is associated with SPR p.Pro143= (c.429G>T)?

SPR p.Pro143= (c.429G>T) is associated with dystonic disorder (ClinVar).

How common is SPR p.Pro143= (c.429G>T) in the general population?

SPR p.Pro143= (c.429G>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

SPR p.Pro143=

c.429G>T · rs778156231 · VCV1534306

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -12	GERP -4.4
Overall
CADD	0.071	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,179,952 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000496% 8/1,613,828 alleles · very rare exomes 7/1,461,668 · genomes 1/152,160 · 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.Pro143=
Coding: c.429G>T
MANE Select: NM_003124
dbSNP: rs778156231
Type: single nucleotide variant
Location: chr2:72888438 (GRCh38)
Gene constraint: LOEUF 1.528 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.71 · 14 PDB
Residue 143: a UniProt-annotated variant site (in drdsprd)

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.Pro143Ala Uncertain significance ★ ⚠ same residue
SPR p.Pro143Arg Uncertain significance ★ ⚠ same residue
SPR p.Pro143Leu 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

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-pro143 (accessed [today's date]).

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