Is ATIC p.Glu514= (c.1542A>G) pathogenic?

ATIC p.Glu514= (c.1542A>G) is classified Likely benign in ATIC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-23). Ultra-rare (popmax 0.0217%, amr); Associated with ATIC-related disorder.

What condition is associated with ATIC p.Glu514= (c.1542A>G)?

ATIC p.Glu514= (c.1542A>G) is associated with ATIC-related disorder (ClinVar).

How common is ATIC p.Glu514= (c.1542A>G) in the general population?

ATIC p.Glu514= (c.1542A>G) is ultra-rare (popmax 0.0217%, amr) (gnomAD).

ATIC p.Glu514=

c.1542A>G · rs138540592 · VCV3053406

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0217%, amr)

Conditions

ATIC-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.197	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.07	GERP -2.1, phastCons 0.13
Overall
CADD	5.894	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0217% Admixed American · 13/60,022 alleles

Filtering AF 0.0127% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0101%

Overall 0.00173% 28/1,614,128 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0217%	4,617
Remaining individualsnot grpmax-eligible	0.0048%	20,837
European (non-Finnish)	0.00102%	98,333

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.Glu514=
Coding: c.1542A>G
MANE Select: NM_004044
dbSNP: rs138540592
Type: single nucleotide variant
Location: chr2:215349132 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 514: the 'aicar formyltransferase' region; a β-strand

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

Disease context

ATIC-related disorder

Similar variants

ATIC p.Glu514Lys Uncertain significance ★ ⚠ same residue
ATIC p.Ser34= Likely benign same condition
ATIC p.Tyr290fs Likely pathogenic ★ same condition
ATIC c.688+3A>G Uncertain significance ★★ same type
ATIC p.Ala140Thr Uncertain significance ★★ ⚠ same type
ATIC p.Ala183Glu Uncertain significance ★★ ⚠ same type
ATIC p.Ala510Thr Uncertain significance ★★ ⚠ same type
ATIC p.His584Arg Uncertain significance ★★ ⚠ same type

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-glu514 (accessed [today's date]).

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