Is AGTPBP1 p.Cys1069Phe (c.3206G>T) pathogenic?

AGTPBP1 p.Cys1069Phe (c.3206G>T) is classified Uncertain significance in AGTPBP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-15). AlphaMissense: likely pathogenic (0.6771); Rare (popmax 0.213%, afr); Associated with neurodegeneration, childhood-onset, with cerebellar atrophy.

What condition is associated with AGTPBP1 p.Cys1069Phe (c.3206G>T)?

AGTPBP1 p.Cys1069Phe (c.3206G>T) is associated with neurodegeneration, childhood-onset, with cerebellar atrophy (ClinVar).

How common is AGTPBP1 p.Cys1069Phe (c.3206G>T) in the general population?

AGTPBP1 p.Cys1069Phe (c.3206G>T) is rare (popmax 0.213%, afr) (gnomAD).

What do computational predictors say about AGTPBP1 p.Cys1069Phe (c.3206G>T)?

AlphaMissense predicts likely pathogenic (score 0.6771) — an in-silico prediction, not a clinical call.

AGTPBP1 p.Cys1069Phe

c.3206G>T · rs148724007 · VCV2438929

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6771 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.213%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

neurodegeneration, childhood-onset, with cerebellar atrophy

Computational evidence

Protein change
AlphaMissense	0.6771	likely pathogenic
REVEL	0.101	moderately benign-leaning
SaProt	LLR -10.70	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.045, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 74 kb · p 7.5e-11 · regional, not allelic
Overall
CADD	26.5	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 0.213% African / African-American · 159/74,758 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.175%

Overall 0.0383% 617/1,610,636 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.213%	470
Middle Eastern	0.199%	503
Admixed American	0.0998%	1,002
Remaining individualsnot grpmax-eligible	0.0947%	1,056
European (non-Finnish)	0.0276%	3,627
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,552
South Asian	0.00221%	45,289

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: AGTPBP1
Protein: p.Cys1069Phe
Coding: c.3206G>T
MANE Select: NM_001330701
dbSNP: rs148724007
Type: single nucleotide variant
Location: chr9:85579056 (GRCh38)
Gene constraint: LOEUF 0.556 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.95
Residue 1069: the peptidase m14 domain; a UniProt-annotated variant site (in condca); a UniProt-annotated variant site (in condca; loss of tubulin deglutamylation; patient cells show lack of protein and excess of tubulin polyglutamylation)

Full AGTPBP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

neurodegeneration, childhood-onset, with cerebellar atrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AGTPBP1 c.-206G>A Uncertain significance ★★ same condition
AGTPBP1 p.Arg174His Uncertain significance ★★ ⚠ same condition
AGTPBP1 c.1303-4238C>G Pathogenic ★ same condition
AGTPBP1 c.2016-2A>G Likely pathogenic ★ same condition
AGTPBP1 c.2335+1G>A Likely pathogenic ★ same condition
AGTPBP1 c.2336-1G>T Pathogenic ★ same condition
AGTPBP1 c.910-1G>A Pathogenic ★ same condition
AGTPBP1 c.-34+1G>A Likely pathogenic ★ 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/agtpbp1-p-cys1069phe (accessed [today's date]).

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