Is ATIC p.Arg79His (c.236G>A) pathogenic?

ATIC p.Arg79His (c.236G>A) is classified Uncertain significance in ATIC (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: ambiguous (0.4422); Ultra-rare (popmax 0.0162%, nfe).

How common is ATIC p.Arg79His (c.236G>A) in the general population?

ATIC p.Arg79His (c.236G>A) is ultra-rare (popmax 0.0162%, nfe) (gnomAD).

What do computational predictors say about ATIC p.Arg79His (c.236G>A)?

AlphaMissense predicts ambiguous (score 0.4422) — an in-silico prediction, not a clinical call.

ATIC p.Arg79His

c.236G>A · rs149652377 · VCV2361995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4422 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0162%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4422	ambiguous
REVEL	0.639	indeterminate
SaProt	LLR -12.59	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.4, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 38 kb · p 0.044 · regional, not allelic
Overall
CADD	32.0	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 0.0162% European (non-Finnish) · 191/1,176,544 alleles

Filtering AF 0.0143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0136%

Overall 0.0129% 207/1,610,076 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0162%	6,160
Remaining individualsnot grpmax-eligible	0.0112%	8,908
Admixed American	0.01%	9,996
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,568
African / African-American	0.00267%	37,397

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.Arg79His
Coding: c.236G>A
MANE Select: NM_004044
dbSNP: rs149652377
Type: single nucleotide variant
Location: chr2:215319677 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 79: the mgs-like domain; the 'imp cyclohydrolase' 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-arg79his (accessed [today's date]).

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