Is TTI2 p.Gly502= (c.1506C>T) pathogenic?

TTI2 p.Gly502= (c.1506C>T) is classified Likely benign in TTI2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-08-01). Ultra-rare (popmax 0.0307%, sas).

How common is TTI2 p.Gly502= (c.1506C>T) in the general population?

TTI2 p.Gly502= (c.1506C>T) is ultra-rare (popmax 0.0307%, sas) (gnomAD).

TTI2 p.Gly502=

c.1506C>T · rs200273292 · VCV764915

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, sas)

⚠ 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
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.5	GERP -3.8
Overall
CADD	4.813	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% South Asian · 28/91,078 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00632% 102/1,613,724 alleles · ultra-rare exomes 91/1,461,536 · genomes 11/152,188 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0307%	3,253
African / African-American	0.016%	6,248
Remaining individualsnot grpmax-eligible	0.0128%	7,811
Admixed American	0.00833%	12,002
East Asian	0.00446%	22,431
European (non-Finnish)	0.00398%	25,101

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.Gly502=
Coding: c.1506C>T
MANE Select: NM_001102401
dbSNP: rs200273292
Type: single nucleotide variant
Location: chr8:33499194 (GRCh38)

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

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-gly502 (accessed [today's date]).

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