Is TTK p.Ala110Pro (c.328G>C) pathogenic?

TTK p.Ala110Pro (c.328G>C) is classified Uncertain significance in TTK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-06). AlphaMissense: likely pathogenic (0.9831); Absent from gnomAD v4.1.

How common is TTK p.Ala110Pro (c.328G>C) in the general population?

TTK p.Ala110Pro (c.328G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTK p.Ala110Pro (c.328G>C)?

AlphaMissense predicts likely pathogenic (score 0.9831) — an in-silico prediction, not a clinical call.

TTK p.Ala110Pro

c.328G>C · VCV4193456

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9831 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.9831	likely pathogenic · top 4% in TTK
REVEL	0.634	indeterminate
SaProt	LLR -15.45	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 36 kb · p 0.03 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: TTK
Protein: p.Ala110Pro
Coding: c.328G>C
MANE Select: NM_003318
Type: single nucleotide variant
Location: chr6:80007997 (GRCh38)
Gene constraint: LOEUF 0.666 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.11 · 78 PDB
Residue 110: an α-helix

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

Similar variants

TTK p.Thr423= Likely benign ★★ same type
TTK p.Ala251Gly Uncertain significance ★ ⚠ same type
TTK p.Ala401Pro Uncertain significance ★ ⚠ same type
TTK p.Ala402Val Uncertain significance ★ ⚠ same type
TTK p.Ala787Gly Uncertain significance ★ ⚠ same type
TTK p.Arg129Cys Uncertain significance ★ ⚠ same type
TTK p.Arg256Pro Uncertain significance ★ ⚠ same type
TTK p.Arg414Gly Uncertain significance ★ ⚠ same type

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/ttk-p-ala110pro (accessed [today's date]).

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