Is ATIC p.Asp191Glu (c.573T>G) pathogenic?

ATIC p.Asp191Glu (c.573T>G) is classified Benign in ATIC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1971); Rare (popmax 0.914%, eas).

How common is ATIC p.Asp191Glu (c.573T>G) in the general population?

ATIC p.Asp191Glu (c.573T>G) is rare (popmax 0.914%, eas) (gnomAD).

What do computational predictors say about ATIC p.Asp191Glu (c.573T>G)?

AlphaMissense predicts likely benign (score 0.1971) — an in-silico prediction, not a clinical call.

ATIC p.Asp191Glu

c.573T>G · rs77239104 · VCV721245

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1971 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.914%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.1971	likely benign
REVEL	0.493	indeterminate
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.92	GERP -0.065, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 38 kb · p 0.044 · regional, not allelic
Overall
CADD	22.2	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 0.914% East Asian · 410/44,880 alleles

Filtering AF 0.841% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.812%

Overall 0.0348% 561/1,614,140 alleles · rare exomes 493/1,461,890 · genomes 68/152,250 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.914%	109
South Asian	0.108%	929
Remaining individualsnot grpmax-eligible	0.072%	1,389
Middle Eastern	0.0165%	6,058
Admixed American	0.00167%	60,004
European (non-Finnish)	0.000508%	196,673

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.Asp191Glu
Coding: c.573T>G
MANE Select: NM_004044
dbSNP: rs77239104
Type: single nucleotide variant
Location: chr2:215326863 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 191: the 'imp cyclohydrolase' region; an α-helix

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-asp191glu (accessed [today's date]).

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