Is ATCAY p.Ile166Val (c.496A>G) pathogenic?

ATCAY p.Ile166Val (c.496A>G) is classified Uncertain significance in ATCAY (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). AlphaMissense: ambiguous (0.4745); Very rare (popmax 0.000848%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATCAY p.Ile166Val (c.496A>G)?

ATCAY p.Ile166Val (c.496A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ATCAY p.Ile166Val (c.496A>G) in the general population?

ATCAY p.Ile166Val (c.496A>G) is very rare (popmax 0.000848%, nfe) (gnomAD).

What do computational predictors say about ATCAY p.Ile166Val (c.496A>G)?

AlphaMissense predicts ambiguous (score 0.4745) — an in-silico prediction, not a clinical call.

ATCAY p.Ile166Val

c.496A>G · VCV3320255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4745 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000848%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4745	ambiguous
REVEL	0.243	benign-leaning
SaProt	LLR -8.87	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 39 kb · p 0.0055 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000848% European (non-Finnish) · 10/1,179,844 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000313%

Overall 0.00062% 10/1,613,844 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.Ile166Val
Coding: c.496A>G
MANE Select: NM_033064
Type: single nucleotide variant
Location: chr19:3907871 (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

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-ile166val (accessed [today's date]).

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