Is ATCAY p.Pro205= (c.615C>A) pathogenic?

ATCAY p.Pro205= (c.615C>A) is classified Benign/Likely benign in ATCAY (ClinVar, Multiple submitters, 3 submitters; last evaluated 2018-07-06). Rare (popmax 0.311%, afr); Associated with Cayman type cerebellar ataxia.

What condition is associated with ATCAY p.Pro205= (c.615C>A)?

ATCAY p.Pro205= (c.615C>A) is associated with Cayman type cerebellar ataxia (ClinVar).

How common is ATCAY p.Pro205= (c.615C>A) in the general population?

ATCAY p.Pro205= (c.615C>A) is rare (popmax 0.311%, afr) (gnomAD).

How is Cerebellar ataxia, Cayman type inherited?

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

ATCAY p.Pro205=

c.615C>A · rs112563476 · VCV735386

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.311%, afr)

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 -20	GERP -5.1
Overall
CADD	0.041	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.311% African / African-American · 232/74,606 alleles

Filtering AF 0.278% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.265%

Overall 0.0185% 295/1,594,022 alleles · rare exomes 177/1,441,764 · genomes 118/152,258 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.311%	322
Middle Eastern	0.0993%	1,007
Remaining individualsnot grpmax-eligible	0.0243%	4,119
Admixed American	0.021%	4,766
European (non-Finnish)	0.00239%	41,793
South Asian	0.00228%	43,897

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.Pro205=
Coding: c.615C>A
MANE Select: NM_033064
dbSNP: rs112563476
Type: single nucleotide variant
Location: chr19:3908338 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.68
Residue 205: 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 p.Pro205Ser Uncertain significance ★ ⚠ same residue
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

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-pro205 (accessed [today's date]).

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