Is TTI1 p.Asp736Val (c.2207A>T) pathogenic?

TTI1 p.Asp736Val (c.2207A>T) is classified Uncertain significance in TTI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely pathogenic (0.6877); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TTI1 p.Asp736Val (c.2207A>T)?

TTI1 p.Asp736Val (c.2207A>T) is associated with Inborn genetic diseases (ClinVar).

How common is TTI1 p.Asp736Val (c.2207A>T) in the general population?

TTI1 p.Asp736Val (c.2207A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTI1 p.Asp736Val (c.2207A>T)?

AlphaMissense predicts likely pathogenic (score 0.6877) — an in-silico prediction, not a clinical call.

TTI1 p.Asp736Val

c.2207A>T · rs2515457064 · VCV3184468

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6877 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6877	likely pathogenic
REVEL	0.601	indeterminate
SaProt	LLR -11.53	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 30 kb · p 0.00063 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTI1
Protein: p.Asp736Val
Coding: c.2207A>T
MANE Select: NM_001303457
dbSNP: rs2515457064
Type: single nucleotide variant
Location: chr20:38011610 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.38 · 3 PDB
Residue 736: 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

Similar variants

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TTI1 p.Arg519Gln Uncertain significance ★★ ⚠ same condition
TTI1 p.Arg724Gly Uncertain significance ★★ ⚠ same condition
TTI1 p.Arg869Cys Uncertain significance ★★ same condition
TTI1 p.Cys86Tyr Uncertain significance ★★ ⚠ same condition
TTI1 p.His229Tyr Uncertain significance ★★ ⚠ same condition
TTI1 p.His513Tyr Uncertain significance ★★ ⚠ same condition
TTI1 p.Ile862Val 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/tti1-p-asp736val (accessed [today's date]).

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