Is TTI1 p.Arg920Trp (c.2758C>T) pathogenic?

TTI1 p.Arg920Trp (c.2758C>T) is classified Uncertain significance in TTI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely benign (0.1457); Ultra-rare (popmax 0.0185%, sas); Associated with Inborn genetic diseases.

What condition is associated with TTI1 p.Arg920Trp (c.2758C>T)?

TTI1 p.Arg920Trp (c.2758C>T) is associated with Inborn genetic diseases (ClinVar).

How common is TTI1 p.Arg920Trp (c.2758C>T) in the general population?

TTI1 p.Arg920Trp (c.2758C>T) is ultra-rare (popmax 0.0185%, sas) (gnomAD).

What do computational predictors say about TTI1 p.Arg920Trp (c.2758C>T)?

AlphaMissense predicts likely benign (score 0.1457) — an in-silico prediction, not a clinical call.

TTI1 p.Arg920Trp

c.2758C>T · rs780927324 · VCV2225460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1457 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0185%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1457	likely benign
REVEL	0.088	moderately benign-leaning
SaProt	LLR -10.33	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.9, phastCons 0.41
Regional constraint	o/e 0.91	unconstrained · MANE · 30 kb · p 0.00063 · regional, not allelic
Overall
CADD	20.7	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 0.0185% South Asian · 14/75,692 alleles

Filtering AF 0.0111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.01%

Overall 0.0106% 160/1,511,510 alleles · ultra-rare exomes 154/1,359,290 · genomes 6/152,220 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0185%	5,407
European (non-Finnish)	0.0123%	8,115
Remaining individualsnot grpmax-eligible	0.0121%	8,238

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: TTI1
Protein: p.Arg920Trp
Coding: c.2758C>T
MANE Select: NM_001303457
dbSNP: rs780927324
Type: single nucleotide variant
Location: chr20:37999223 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.38 · 3 PDB
Residue 920: a UniProt-annotated variant site (in nedmim; likely pathogenic)

Full TTI1 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

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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/tti1-p-arg920trp (accessed [today's date]).

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