Is ATIC p.Asn94Ser (c.281A>G) pathogenic?

ATIC p.Asn94Ser (c.281A>G) is classified Benign in ATIC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-15). AlphaMissense: likely benign (0.0562); Low-frequency (popmax 1.74%, afr).

How common is ATIC p.Asn94Ser (c.281A>G) in the general population?

ATIC p.Asn94Ser (c.281A>G) is low-frequency (popmax 1.74%, afr) (gnomAD).

What do computational predictors say about ATIC p.Asn94Ser (c.281A>G)?

AlphaMissense predicts likely benign (score 0.0562) — an in-silico prediction, not a clinical call.

ATIC p.Asn94Ser

c.281A>G · rs75086019 · VCV791888

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0562 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.74%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0562	likely benign
REVEL	0.24	benign-leaning
SaProt	LLR -1.85	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 -1.1	GERP -4.7
Regional constraint	o/e 1.07	unconstrained · MANE · 38 kb · p 0.044 · regional, not allelic
Overall
CADD	0.625	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 1.74% African / African-American · 1,303/74,908 alleles

Filtering AF 1.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.63%

Overall 0.0926% 1,490/1,608,548 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.74%	57
Remaining individualsnot grpmax-eligible	0.0963%	1,039
Admixed American	0.08%	1,250
South Asian	0.0682%	1,467
Middle Eastern	0.033%	3,026
East Asian	0.00223%	44,840
European (non-Finnish)	0.00119%	83,926

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.Asn94Ser
Coding: c.281A>G
MANE Select: NM_004044
dbSNP: rs75086019
Type: single nucleotide variant
Location: chr2:215319722 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 94: the mgs-like domain; 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-asn94ser (accessed [today's date]).

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