Is ATIC p.Gly500Asp (c.1499G>A) pathogenic?

ATIC p.Gly500Asp (c.1499G>A) is classified Benign/Likely benign in ATIC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-25). AlphaMissense: ambiguous (0.4073); Low-frequency (popmax 2.41%, afr); Associated with AICA-ribosiduria.

What condition is associated with ATIC p.Gly500Asp (c.1499G>A)?

ATIC p.Gly500Asp (c.1499G>A) is associated with AICA-ribosiduria (ClinVar).

How common is ATIC p.Gly500Asp (c.1499G>A) in the general population?

ATIC p.Gly500Asp (c.1499G>A) is low-frequency (popmax 2.41%, afr) (gnomAD).

How is AICA-ribosiduria inherited?

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

What do computational predictors say about ATIC p.Gly500Asp (c.1499G>A)?

AlphaMissense predicts ambiguous (score 0.4073) — an in-silico prediction, not a clinical call.

ATIC p.Gly500Asp

c.1499G>A · rs76414987 · VCV775810

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

ambiguous

0.4073 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.41%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

AICA-ribosiduria

Computational evidence

Protein change
AlphaMissense	0.4073	ambiguous
REVEL	0.646	pathogenic-leaning
SaProt	LLR -12.26	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 38 kb · p 0.044 · regional, not allelic
Overall
CADD	27.1	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 2.41% African / African-American · 1,808/75,044 alleles

Filtering AF 2.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.28%

Overall 0.13% 2,103/1,614,148 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.41%	42
Admixed American	0.22%	455
Remaining individualsnot grpmax-eligible	0.163%	613
Middle Eastern	0.0495%	2,021
South Asian	0.00769%	13,011
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,800
European (non-Finnish)	0.00415%	24,082

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: ATIC
Protein: p.Gly500Asp
Coding: c.1499G>A
MANE Select: NM_004044
dbSNP: rs76414987
Type: single nucleotide variant
Location: chr2:215346937 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 500: 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.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-gly500asp (accessed [today's date]).

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