Is TTBK2 p.Pro976= (c.2928A>T) pathogenic?

TTBK2 p.Pro976= (c.2928A>T) is classified Uncertain significance in TTBK2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Absent from gnomAD v4.1; Associated with spinocerebellar ataxia type 11.

What condition is associated with TTBK2 p.Pro976= (c.2928A>T)?

TTBK2 p.Pro976= (c.2928A>T) is associated with spinocerebellar ataxia type 11 (ClinVar).

How common is TTBK2 p.Pro976= (c.2928A>T) in the general population?

TTBK2 p.Pro976= (c.2928A>T) is absent from gnomAD v4.1 (gnomAD).

How is Spinocerebellar ataxia type 11 inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

TTBK2 p.Pro976=

c.2928A>T · rs1567000293 · VCV888521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

spinocerebellar ataxia type 11

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 -0.15	GERP -4.3, phastCons 0.79
Overall
CADD	5.397	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTBK2
Protein: p.Pro976=
Coding: c.2928A>T
MANE Select: NM_173500
dbSNP: rs1567000293
Type: single nucleotide variant
Location: chr15:42752318 (GRCh38)
Gene constraint: LOEUF 0.326 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.55 · 7 PDB

Full TTBK2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

spinocerebellar ataxia type 11 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Spinocerebellar ataxia type 11 (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood, Elderly

Similar variants

TTBK2 p.Ala102Ser Uncertain significance ★★ ⚠ same condition
TTBK2 p.Ala197Thr Uncertain significance ★★ ⚠ same condition
TTBK2 p.Ala644Pro Uncertain significance ★★ ⚠ same condition
TTBK2 p.Arg1162Cys Uncertain significance ★★ same condition
TTBK2 p.Arg181Ter Uncertain significance ★★ same condition
TTBK2 p.Arg454Cys Uncertain significance ★★ ⚠ same condition
TTBK2 p.Arg764Lys Uncertain significance ★★ ⚠ same condition
TTBK2 p.Asn391Lys 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/ttbk2-p-pro976 (accessed [today's date]).

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