Is ATIC p.Val319Ile (c.955G>A) pathogenic?

ATIC p.Val319Ile (c.955G>A) is classified Benign in ATIC (ClinVar, Single submitter, 3 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.0791); Low-frequency (popmax 1.81%, sas).

How common is ATIC p.Val319Ile (c.955G>A) in the general population?

ATIC p.Val319Ile (c.955G>A) is low-frequency (popmax 1.81%, sas) (gnomAD).

What do computational predictors say about ATIC p.Val319Ile (c.955G>A)?

AlphaMissense predicts likely benign (score 0.0791) — an in-silico prediction, not a clinical call.

ATIC p.Val319Ile

c.955G>A · rs147114143 · VCV728731

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0791 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.81%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0791	likely benign
REVEL	0.19	benign-leaning
SaProt	LLR -4.41	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 0.2	GERP -4.7, phastCons 0.63
Regional constraint	o/e 1.07	unconstrained · MANE · 38 kb · p 0.044 · regional, not allelic
Overall
CADD	4.738	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 1.81% South Asian · 1,647/91,070 alleles

Filtering AF 1.74% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.71%

Overall 0.114% 1,833/1,613,576 alleles · low-frequency exomes 1,720/1,461,344 · genomes 113/152,232 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	1.81%	55
Remaining individualsnot grpmax-eligible	0.146%	687
Admixed American	0.07%	1,428
Middle Eastern	0.033%	3,029
East Asian	0.0067%	14,921
European (non-Finnish)	0.00398%	25,101
African / African-American	0.00133%	75,014

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.Val319Ile
Coding: c.955G>A
MANE Select: NM_004044
dbSNP: rs147114143
Type: single nucleotide variant
Location: chr2:215334951 (GRCh38)
Gene constraint: LOEUF 1.044 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.46 · 5 PDB
Residue 319: the 'aicar formyltransferase' region; a β-strand

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-val319ile (accessed [today's date]).

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