Is ATCAY p.Thr142= (c.426G>A) pathogenic?

ATCAY p.Thr142= (c.426G>A) is classified Benign/Likely benign in ATCAY (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-01). Low-frequency (popmax 1.55%, mid); Associated with Cayman type cerebellar ataxia.

What condition is associated with ATCAY p.Thr142= (c.426G>A)?

ATCAY p.Thr142= (c.426G>A) is associated with Cayman type cerebellar ataxia (ClinVar).

How common is ATCAY p.Thr142= (c.426G>A) in the general population?

ATCAY p.Thr142= (c.426G>A) is low-frequency (popmax 1.55%, mid) (gnomAD).

How is Cerebellar ataxia, Cayman type inherited?

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

ATCAY p.Thr142=

c.426G>A · rs373080859 · VCV788138

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.55%, mid)

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 -14	GERP -4.6
Overall
CADD	0.033	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.55% Middle Eastern · 94/6,062 alleles

Filtering AF 1.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 0.0819% 1,322/1,613,982 alleles · low-frequency

Ancestry group	Frequency	1 in
Middle Easterngrpmax	1.55%	64
South Asian	0.663%	151
Remaining individualsnot grpmax-eligible	0.138%	727
Ashkenazi Jewishnot grpmax-eligible	0.0743%	1,345
Admixed American	0.05%	2,001
European (non-Finnish)	0.0388%	2,576
Finnishnot grpmax-eligible	0.025%	4,000
African / African-American	0.0133%	7,507
East Asian	0.00446%	22,440

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.Thr142=
Coding: c.426G>A
MANE Select: NM_033064
dbSNP: rs373080859
Type: single nucleotide variant
Location: chr19:3907801 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.68

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-thr142 (accessed [today's date]).

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