Is TTI1 p.Ala207Asp (c.620C>A) pathogenic?

TTI1 p.Ala207Asp (c.620C>A) is classified Uncertain significance in TTI1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely pathogenic (0.9645); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with TTI1 p.Ala207Asp (c.620C>A)?

TTI1 p.Ala207Asp (c.620C>A) is associated with Inborn genetic diseases (ClinVar).

How common is TTI1 p.Ala207Asp (c.620C>A) in the general population?

TTI1 p.Ala207Asp (c.620C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTI1 p.Ala207Asp (c.620C>A)?

AlphaMissense predicts likely pathogenic (score 0.9645) — an in-silico prediction, not a clinical call.

TTI1 p.Ala207Asp

c.620C>A · rs2515465730 · VCV3184482

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9645 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9645	likely pathogenic · top 1% in TTI1
REVEL	0.572	indeterminate
SaProt	LLR -10.23	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 30 kb · p 0.00063 · regional, not allelic
Overall
CADD	26.4	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.Ala207Asp
Coding: c.620C>A
MANE Select: NM_001303457
dbSNP: rs2515465730
Type: single nucleotide variant
Location: chr20:38013197 (GRCh38)
Gene constraint: LOEUF 0.78 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.38 · 3 PDB
Residue 207: 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.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-ala207asp (accessed [today's date]).

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