Is ATCAY p.Ser334= (c.1002C>T) pathogenic?

ATCAY p.Ser334= (c.1002C>T) is classified Uncertain significance in ATCAY (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-13). Very rare (popmax 0.00833%, amr); Associated with Cayman type cerebellar ataxia.

What condition is associated with ATCAY p.Ser334= (c.1002C>T)?

ATCAY p.Ser334= (c.1002C>T) is associated with Cayman type cerebellar ataxia (ClinVar).

How common is ATCAY p.Ser334= (c.1002C>T) in the general population?

ATCAY p.Ser334= (c.1002C>T) is very rare (popmax 0.00833%, 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.Ser334=

c.1002C>T · rs767813874 · VCV892890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00833%, 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 -7.7	GERP -2.4
Overall
CADD	3.185	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00833% Admixed American · 5/60,010 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00136% 22/1,613,888 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
East Asian	0.00223%	44,876
Remaining individualsnot grpmax-eligible	0.0016%	62,482
African / African-American	0.00133%	75,054
European (non-Finnish)	0.0011%	90,755
South Asian	0.0011%	91,080

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.Ser334=
Coding: c.1002C>T
MANE Select: NM_033064
dbSNP: rs767813874
Type: single nucleotide variant
Location: chr19:3918806 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.68
Residue 334: the 'mediates interaction with gls' region; the 'disordered' 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-ser334 (accessed [today's date]).

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