Is ATCAY p.Thr239= (c.717G>A) pathogenic?

ATCAY p.Thr239= (c.717G>A) is classified Conflicting classifications of pathogenicity in ATCAY (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2018-04-02). Ultra-rare (popmax 0.0184%, amr); Associated with Cayman type cerebellar ataxia.

What condition is associated with ATCAY p.Thr239= (c.717G>A)?

ATCAY p.Thr239= (c.717G>A) is associated with Cayman type cerebellar ataxia (ClinVar).

How common is ATCAY p.Thr239= (c.717G>A) in the general population?

ATCAY p.Thr239= (c.717G>A) is ultra-rare (popmax 0.0184%, amr) (gnomAD).

How is Cerebellar ataxia, Cayman type inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

ATCAY p.Thr239=

c.717G>A · rs768556456 · VCV329150

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0184%, amr)

Conditions

Cayman type cerebellar ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.4	GERP -4.3
Overall
CADD	3.344	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0184% Admixed American · 11/59,944 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00786%

Overall 0.00632% 102/1,613,516 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0184%	5,449
Remaining individualsnot grpmax-eligible	0.0128%	7,808
European (non-Finnish)	0.0067%	14,934
East Asian	0.00223%	44,850
Finnishnot grpmax-eligible	0.00156%	63,938
African / African-American	0.00133%	74,920
South Asian	0.0011%	91,036

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: ATCAY
Protein: p.Thr239=
Coding: c.717G>A
MANE Select: NM_033064
dbSNP: rs768556456
Type: single nucleotide variant
Location: chr19:3909555 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.68
Residue 239: the cral-trio domain; the 'mediates interaction with gls' region

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

Disease context

Cayman type cerebellar ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Cerebellar ataxia, Cayman type (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

ATCAY c.*3332C>A Uncertain significance ★★ same condition
ATCAY p.Ala148Thr Uncertain significance ★★ ⚠ same condition
ATCAY p.Val124Met Uncertain significance ★★ ⚠ same condition
ATCAY c.1074-14T>C Benign ★★ same condition
ATCAY c.137-11T>C Likely benign ★★ same condition
ATCAY c.545-65T>C Benign ★★ same condition
ATCAY c.545-8C>T Benign/Likely benign ★★ same condition
ATCAY c.647+10C>T Benign/Likely benign ★★ 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/atcay-p-thr239 (accessed [today's date]).

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