Is SPOP p.Val91= (c.273C>T) pathogenic?

SPOP p.Val91= (c.273C>T) is classified Uncertain significance in SPOP (ClinVar, No assertion criteria, 1 submitter). Very rare (popmax 6.84e-05%); Associated with prostate cancer.

What condition is associated with SPOP p.Val91= (c.273C>T)?

SPOP p.Val91= (c.273C>T) is associated with prostate cancer (ClinVar).

How common is SPOP p.Val91= (c.273C>T) in the general population?

SPOP p.Val91= (c.273C>T) is very rare (popmax 6.84e-05%) (gnomAD).

SPOP p.Val91=

c.273C>T · rs2072166000 · VCV694223

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Conditions

prostate cancer

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5.2	GERP -0.18, phastCons 1
Overall
CADD	10.84	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,870 alleles · very rare

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: SPOP
Protein: p.Val91=
Coding: c.273C>T
MANE Select: NM_001007228
dbSNP: rs2072166000
Type: single nucleotide variant
Location: chr17:49619313 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.38 · 36 PDB
Residue 91: the math domain; the 'required for nuclear localization' region; a β-strand

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

Disease context

prostate cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SPOP c.353-1G>A Uncertain significance ★ same condition
SPOP p.Arg99Trp Conflicting classifications of pathogenicity ★ ⚠ same condition
SPOP p.Glu160Lys Conflicting classifications of pathogenicity ★ ⚠ same condition
SPOP c.201-1G>C Uncertain significance same condition
SPOP c.201-2A>G Uncertain significance same condition
SPOP c.353-11C>T Uncertain significance same condition
SPOP c.353-17T>A Uncertain significance same condition
SPOP c.353-17T>G 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/spop-p-val91 (accessed [today's date]).

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