Is ATIC p.Lys357fs (c.1070del) pathogenic?

ATIC p.Lys357fs (c.1070del) is classified Likely pathogenic in ATIC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-30). Associated with AICA-ribosiduria.

What condition is associated with ATIC p.Lys357fs (c.1070del)?

ATIC p.Lys357fs (c.1070del) is associated with AICA-ribosiduria (ClinVar).

How is AICA-ribosiduria inherited?

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

ATIC p.Lys357fs

c.1070del · VCV4845921

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

AICA-ribosiduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 11 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.84	GERP -2.8, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ATIC
Protein: p.Lys357fs
Coding: c.1070del
MANE Select: NM_004044
Type: Deletion
Location: chr2:215336092 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 357: the 'aicar formyltransferase' region

Full ATIC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AICA-ribosiduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For AICA-ribosiduria (Orphanet):

Inheritance: Autosomal recessive
Onset: Antenatal, Infancy, Neonatal

Similar variants

ATIC p.Pro82fs Likely pathogenic ★ same condition
ATIC p.Lys357Glu Uncertain significance ★ ⚠ same residue
ATIC p.Phe265fs Uncertain significance same condition
ATIC p.Ala183Glu Uncertain significance ★★ ⚠ same condition
ATIC p.His584Arg Uncertain significance ★★ ⚠ same condition
ATIC c.1098+60C>G Benign ★★ same condition
ATIC c.1228-30A>G Benign ★★ same condition
ATIC c.147-111A>T 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/atic-p-lys357fs (accessed [today's date]).

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