Is TTI2 p.Val150Ile (c.448G>A) pathogenic?

TTI2 p.Val150Ile (c.448G>A) is classified Likely benign in TTI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-03). AlphaMissense: likely benign (0.0773); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with TTI2 p.Val150Ile (c.448G>A)?

TTI2 p.Val150Ile (c.448G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TTI2 p.Val150Ile (c.448G>A) in the general population?

TTI2 p.Val150Ile (c.448G>A) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about TTI2 p.Val150Ile (c.448G>A)?

AlphaMissense predicts likely benign (score 0.0773) — an in-silico prediction, not a clinical call.

TTI2 p.Val150Ile

c.448G>A · rs1437413589 · VCV3184490

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0773 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0773	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -7.55	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.4	GERP -2.5
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.23 · regional, not allelic
Overall
CADD	0.041	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,026 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,614,184 alleles · very rare exomes 3/1,461,894 · genomes 0/152,290 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,026
European (non-Finnish)	0.000169%	590,026

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.Val150Ile
Coding: c.448G>A
MANE Select: NM_001102401
dbSNP: rs1437413589
Type: single nucleotide variant
Location: chr8:33512166 (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

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TTI2 p.Thr232Ile Uncertain significance ★★ ⚠ same condition
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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-val150ile (accessed [today's date]).

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