Is ATCAY p.Pro205Ser (c.613C>T) pathogenic?

ATCAY p.Pro205Ser (c.613C>T) is classified Uncertain significance in ATCAY (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-13). AlphaMissense: likely benign (0.0995); Very rare (popmax 0.00175%, amr); Associated with Inborn genetic diseases.

What condition is associated with ATCAY p.Pro205Ser (c.613C>T)?

ATCAY p.Pro205Ser (c.613C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATCAY p.Pro205Ser (c.613C>T) in the general population?

ATCAY p.Pro205Ser (c.613C>T) is very rare (popmax 0.00175%, amr) (gnomAD).

What do computational predictors say about ATCAY p.Pro205Ser (c.613C>T)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

ATCAY p.Pro205Ser

c.613C>T · rs1349281740 · VCV2266362

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00175%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -8.87	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.2	GERP -4.2, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 39 kb · p 0.0055 · regional, not allelic
Overall
CADD	16.11	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00175% Admixed American · 1/57,260 alleles

Overall 6.93e-05% 1/1,442,148 alleles · very rare

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.Pro205Ser
Coding: c.613C>T
MANE Select: NM_033064
dbSNP: rs1349281740
Type: single nucleotide variant
Location: chr19:3908336 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATCAY p.Pro205= Benign/Likely benign ★★ same residue
ATCAY p.Ala148Thr Uncertain significance ★★ ⚠ same condition
ATCAY p.Ala149Thr Uncertain significance ★★ ⚠ same condition
ATCAY p.Val124Met Uncertain significance ★★ ⚠ same condition
ATCAY p.Ala125Val Uncertain significance ★ ⚠ same condition
ATCAY p.Ala127Val Uncertain significance ★ ⚠ same condition
ATCAY p.Ala195Thr Uncertain significance ★ ⚠ same condition
ATCAY p.Ala56Val Uncertain significance ★ ⚠ 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-pro205ser (accessed [today's date]).

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