Is TTI2 p.Ala503Thr (c.1507G>A) pathogenic?

TTI2 p.Ala503Thr (c.1507G>A) is classified Likely benign in TTI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-20). AlphaMissense: likely benign (0.0651); Ultra-rare (popmax 0.0114%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TTI2 p.Ala503Thr (c.1507G>A)?

TTI2 p.Ala503Thr (c.1507G>A) is associated with Inborn genetic diseases (ClinVar).

How common is TTI2 p.Ala503Thr (c.1507G>A) in the general population?

TTI2 p.Ala503Thr (c.1507G>A) is ultra-rare (popmax 0.0114%, nfe) (gnomAD).

What do computational predictors say about TTI2 p.Ala503Thr (c.1507G>A)?

AlphaMissense predicts likely benign (score 0.0651) — an in-silico prediction, not a clinical call.

TTI2 p.Ala503Thr

c.1507G>A · VCV3463557

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0651 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0114%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
AlphaMissense	0.0651	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -5.89	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -8.8	GERP -3.8
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.23 · regional, not allelic
Overall
CADD	0.142	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 0.0114% European (non-Finnish) · 134/1,179,658 alleles

Filtering AF 0.00978% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00913%

Overall 0.0093% 150/1,613,712 alleles · ultra-rare exomes 139/1,461,452 · genomes 11/152,260 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0114%	8,803
Remaining individualsnot grpmax-eligible	0.0112%	8,928
East Asian	0.00669%	14,956
African / African-American	0.00533%	18,758
Admixed American	0.00333%	30,003

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.Ala503Thr
Coding: c.1507G>A
MANE Select: NM_001102401
Type: single nucleotide variant
Location: chr8:33499193 (GRCh38)

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

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-ala503thr (accessed [today's date]).

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