Is TTI2 p.Leu266= (c.796C>T) pathogenic?

TTI2 p.Leu266= (c.796C>T) is classified Likely benign in TTI2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-10). Ultra-rare (popmax 0.0165%, mid); Associated with TTI2-related disorder.

What condition is associated with TTI2 p.Leu266= (c.796C>T)?

TTI2 p.Leu266= (c.796C>T) is associated with TTI2-related disorder (ClinVar).

How common is TTI2 p.Leu266= (c.796C>T) in the general population?

TTI2 p.Leu266= (c.796C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

TTI2 p.Leu266=

c.796C>T · rs765413522 · VCV3042945

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

TTI2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.82	GERP 0.73, phastCons 1
Overall
CADD	9.377	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Overall 0.000248% 4/1,614,120 alleles · ultra-rare exomes 3/1,461,890 · genomes 1/152,230 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0016%	62,504
African / African-American	0.00133%	75,032
European (non-Finnish)	8.47e-05%	1,180,040

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: TTI2
Protein: p.Leu266=
Coding: c.796C>T
MANE Select: NM_001102401
dbSNP: rs765413522
Type: single nucleotide variant
Location: chr8:33509784 (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

TTI2-related disorder

Similar variants

TTI2 p.Leu266Val Uncertain significance ★ ⚠ same residue
TTI2 p.Asp317Val Pathogenic ★ same condition
TTI2 p.Phe229= Likely benign same condition
TTI2 p.Arg334Gln Uncertain significance ★★ ⚠ same type
TTI2 p.Arg355His Uncertain significance ★★ ⚠ same type
TTI2 p.Arg379Trp Uncertain significance ★★ ⚠ same type
TTI2 p.Gly190Val Uncertain significance ★★ ⚠ same type
TTI2 p.Pro149Leu 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/tti2-p-leu266 (accessed [today's date]).

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