Is SPR p.Ter262= (c.785A>G) pathogenic?

SPR p.Ter262= (c.785A>G) is classified Benign in SPR (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-02). Low-frequency (popmax 1.33%, afr); Associated with dystonic disorder.

What condition is associated with SPR p.Ter262= (c.785A>G)?

SPR p.Ter262= (c.785A>G) is associated with dystonic disorder, dopa-responsive dystonia due to sepiapterin reductase deficiency (ClinVar).

How common is SPR p.Ter262= (c.785A>G) in the general population?

SPR p.Ter262= (c.785A>G) is low-frequency (popmax 1.33%, afr) (gnomAD).

SPR p.Ter262=

c.785A>G · rs145082655 · VCV412652

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

low-frequency (popmax 1.33%, afr)

Conditions

dystonic disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.4	GERP -0.036, phastCons 1
Overall
CADD	9.565	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.33% African / African-American · 995/75,062 alleles

Filtering AF 1.26% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.23%

Overall 0.0736% 1,188/1,614,228 alleles · low-frequency exomes 660/1,461,892 · genomes 528/152,336 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.33%	75
Middle Eastern	0.181%	551
Remaining individualsnot grpmax-eligible	0.123%	812
Admixed American	0.0466%	2,144
European (non-Finnish)	0.00644%	15,527
South Asian	0.0011%	91,086

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.Ter262=
Coding: c.785A>G
MANE Select: NM_003124
dbSNP: rs145082655
Type: single nucleotide variant
Location: chr2:72891536 (GRCh38)
Gene constraint: LOEUF 1.528 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.71 · 14 PDB

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

Also linked: dopa-responsive dystonia due to sepiapterin reductase deficiency

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-ter262 (accessed [today's date]).

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