Is TTI2 p.Thr232Ala (c.694A>G) pathogenic?

TTI2 p.Thr232Ala (c.694A>G) is classified Uncertain significance in TTI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.169); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TTI2 p.Thr232Ala (c.694A>G)?

TTI2 p.Thr232Ala (c.694A>G) is associated with Inborn genetic diseases (ClinVar).

How common is TTI2 p.Thr232Ala (c.694A>G) in the general population?

TTI2 p.Thr232Ala (c.694A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTI2 p.Thr232Ala (c.694A>G)?

AlphaMissense predicts likely benign (score 0.169) — an in-silico prediction, not a clinical call.

TTI2 p.Thr232Ala

c.694A>G · VCV4193434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.169 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.169	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -8.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>A here scores Δ0.45 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.23 · regional, not allelic
Overall
CADD	22.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: TTI2
Protein: p.Thr232Ala
Coding: c.694A>G
MANE Select: NM_001102401
Type: single nucleotide variant
Location: chr8:33509886 (GRCh38)
Gene constraint: LOEUF 0.758 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.85 · 2 PDB

Full TTI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTI2 p.Thr232Ile Uncertain significance ★★ ⚠ same residue
TTI2 p.Arg334Gln Uncertain significance ★★ ⚠ same condition
TTI2 p.Arg355His Uncertain significance ★★ ⚠ same condition
TTI2 p.Arg379Trp Uncertain significance ★★ ⚠ same condition
TTI2 p.Gly190Val Uncertain significance ★★ ⚠ same condition
TTI2 p.Pro149Leu Uncertain significance ★★ ⚠ same condition
TTI2 p.Thr237Ala Uncertain significance ★★ ⚠ same condition
TTI2 p.Pro367Leu Pathogenic ★ ⚠ 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/tti2-p-thr232ala (accessed [today's date]).

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