Is SPR p.Ser243= (c.729C>T) pathogenic?

SPR p.Ser243= (c.729C>T) is classified Likely benign in SPR (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-18). Very rare (popmax 8.47e-05%, nfe); Associated with dystonic disorder.

What condition is associated with SPR p.Ser243= (c.729C>T)?

SPR p.Ser243= (c.729C>T) is associated with dystonic disorder (ClinVar).

How common is SPR p.Ser243= (c.729C>T) in the general population?

SPR p.Ser243= (c.729C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

SPR p.Ser243=

c.729C>T · rs376387677 · VCV1095636

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, 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 0.085	GERP -2.3, phastCons 0.002
Overall
CADD	7.317	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,046 alleles

Overall 0.000137% 2/1,461,894 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)grpmax	8.47e-05%	1,180,045

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser243=
Coding: c.729C>T
MANE Select: NM_003124
dbSNP: rs376387677
Type: single nucleotide variant
Location: chr2:72891480 (GRCh38)
Gene constraint: LOEUF 1.528 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.71 · 14 PDB
Residue 243: a UniProt-annotated variant site (in drdsprd); 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.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
SPR c.304+5G>C 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/spr-p-ser243 (accessed [today's date]).

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