Is ATIC p.Ala44fs (c.131delinsGCA) pathogenic?

ATIC p.Ala44fs (c.131delinsGCA) is classified Conflicting classifications of pathogenicity in ATIC (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-11-18). No gnomAD frequency available for this variant; Associated with AICA-ribosiduria.

What condition is associated with ATIC p.Ala44fs (c.131delinsGCA)?

ATIC p.Ala44fs (c.131delinsGCA) is associated with AICA-ribosiduria (ClinVar).

How common is ATIC p.Ala44fs (c.131delinsGCA) in the general population?

ATIC p.Ala44fs (c.131delinsGCA) is no gnomAD frequency available for this variant (gnomAD).

How is AICA-ribosiduria inherited?

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

ATIC p.Ala44fs

c.131delinsGCA · rs2105985030 · VCV2439310

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.8	GERP 2.1, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ATIC
Protein: p.Ala44fs
Coding: c.131delinsGCA
MANE Select: NM_004044
dbSNP: rs2105985030
Type: Indel
Location: chr2:215312609 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 44: the mgs-like domain; the 'imp cyclohydrolase' region; a turn

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.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
ATIC c.1503+48A>T Benign ★★ same condition
ATIC c.380-18G>A Likely benign ★★ same condition
ATIC c.380-19A>C 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-ala44fs (accessed [today's date]).

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