Is ATIC p.Glu533Lys (c.1597G>A) pathogenic?

ATIC p.Glu533Lys (c.1597G>A) is classified Likely benign in ATIC (ClinVar, Single submitter, 2 submitters; last evaluated 2025-09-27). AlphaMissense: likely benign (0.1103); Rare (popmax 0.414%, afr).

How common is ATIC p.Glu533Lys (c.1597G>A) in the general population?

ATIC p.Glu533Lys (c.1597G>A) is rare (popmax 0.414%, afr) (gnomAD).

What do computational predictors say about ATIC p.Glu533Lys (c.1597G>A)?

AlphaMissense predicts likely benign (score 0.1103) — an in-silico prediction, not a clinical call.

ATIC p.Glu533Lys

c.1597G>A · rs145563811 · VCV722929

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1103 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.414%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1103	likely benign
REVEL	0.255	benign-leaning
SaProt	LLR -5.54	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.5	GERP 2.7, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 38 kb · p 0.044 · regional, not allelic
Overall
CADD	21.8	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 0.414% African / African-American · 311/75,068 alleles

Filtering AF 0.376% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.362%

Overall 0.0212% 343/1,614,160 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.414%	241
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0272%	3,677
Admixed American	0.015%	6,669
South Asian	0.00329%	30,359
European (non-Finnish)	8.47e-05%	1,180,006

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.Glu533Lys
Coding: c.1597G>A
MANE Select: NM_004044
dbSNP: rs145563811
Type: single nucleotide variant
Location: chr2:215349187 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 533: the 'aicar formyltransferase' region

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

Similar variants

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
ATIC p.Ile491Val Uncertain significance ★★ ⚠ same type
ATIC p.Val154Ala Uncertain significance ★★ ⚠ same type
FN1 p.Ala2470Pro 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-glu533lys (accessed [today's date]).

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