Is TTI2 p.Arg344Trp (c.1030C>T) pathogenic?

TTI2 p.Arg344Trp (c.1030C>T) is classified Uncertain significance in TTI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-26). AlphaMissense: likely benign (0.1303); Ultra-rare (popmax 0.0353%, nfe); Associated with Inborn genetic diseases.

What condition is associated with TTI2 p.Arg344Trp (c.1030C>T)?

TTI2 p.Arg344Trp (c.1030C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TTI2 p.Arg344Trp (c.1030C>T) in the general population?

TTI2 p.Arg344Trp (c.1030C>T) is ultra-rare (popmax 0.0353%, nfe) (gnomAD).

What do computational predictors say about TTI2 p.Arg344Trp (c.1030C>T)?

AlphaMissense predicts likely benign (score 0.1303) — an in-silico prediction, not a clinical call.

TTI2 p.Arg344Trp

c.1030C>T · rs137898652 · VCV3184486

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1303 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0353%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1303	likely benign
REVEL	0.186	benign-leaning
SaProt	LLR -9.86	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 9.9	GERP 1.7, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 13 kb · p 0.23 · regional, not allelic
Overall
CADD	27.8	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

Grpmax group 0.0353% European (non-Finnish) · 416/1,180,030 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0313%

Overall 0.0281% 454/1,613,990 alleles · ultra-rare exomes 424/1,461,840 · genomes 30/152,150 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0353%	2,837
East Asian	0.0134%	7,482
South Asian	0.0121%	8,280
Remaining individualsnot grpmax-eligible	0.0112%	8,926
African / African-American	0.00801%	12,484
Admixed American	0.00667%	14,994
Finnishnot grpmax-eligible	0.00468%	21,347
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Arg344Trp
Coding: c.1030C>T
MANE Select: NM_001102401
dbSNP: rs137898652
Type: single nucleotide variant
Location: chr8:33503833 (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.Arg344Gln Benign ★★ 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.Thr232Ile Uncertain significance ★★ ⚠ same condition
TTI2 p.Thr237Ala Uncertain significance ★★ ⚠ 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-arg344trp (accessed [today's date]).

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