Is ATCAY p.Val193Ile (c.577G>A) pathogenic?

ATCAY p.Val193Ile (c.577G>A) is classified Uncertain significance in ATCAY (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-27). AlphaMissense: likely benign (0.157); Very rare (popmax 0.00689%, eas); Associated with Inborn genetic diseases.

What condition is associated with ATCAY p.Val193Ile (c.577G>A)?

ATCAY p.Val193Ile (c.577G>A) is associated with Inborn genetic diseases (ClinVar).

How common is ATCAY p.Val193Ile (c.577G>A) in the general population?

ATCAY p.Val193Ile (c.577G>A) is very rare (popmax 0.00689%, eas) (gnomAD).

What do computational predictors say about ATCAY p.Val193Ile (c.577G>A)?

AlphaMissense predicts likely benign (score 0.157) — an in-silico prediction, not a clinical call.

ATCAY p.Val193Ile

c.577G>A · rs777360536 · VCV2562630

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.157 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00689%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.157	likely benign
REVEL	0.295	indeterminate
SaProt	LLR -9.80	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.6	GERP 2.5, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 39 kb · p 0.0055 · regional, not allelic
Overall
CADD	29.6	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 0.00689% East Asian · 3/43,558 alleles

Filtering AF 0.00183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00105%

Overall 0.00239% 38/1,586,760 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00813%	12,294
East Asiangrpmax	0.00689%	14,519
African / African-American	0.00538%	18,579
South Asian	0.00345%	28,970
European (non-Finnish)	0.00189%	53,029
Admixed American	0.00178%	56,052

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val193Ile
Coding: c.577G>A
MANE Select: NM_033064
dbSNP: rs777360536
Type: single nucleotide variant
Location: chr19:3908300 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 70.68
Residue 193: 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.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
ATCAY p.Arg155Gln 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-val193ile (accessed [today's date]).

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