Is ITPA p.Pro97= (c.291T>G) pathogenic?

ITPA p.Pro97= (c.291T>G) is classified Benign/Likely benign in ITPA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-03-01). Rare (popmax 0.578%, amr); Associated with inosine triphosphatase deficiency.

What condition is associated with ITPA p.Pro97= (c.291T>G)?

ITPA p.Pro97= (c.291T>G) is associated with inosine triphosphatase deficiency (ClinVar).

How common is ITPA p.Pro97= (c.291T>G) in the general population?

ITPA p.Pro97= (c.291T>G) is rare (popmax 0.578%, amr) (gnomAD).

ITPA p.Pro97=

c.291T>G · rs145329644 · VCV464830

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.578%, amr)

Conditions

inosine triphosphatase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.41, phastCons 1
Overall
CADD	11.57	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.578% Admixed American · 347/60,016 alleles

Filtering AF 0.528% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.508%

Overall 0.0262% 423/1,613,844 alleles · rare exomes 297/1,461,520 · genomes 126/152,324 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.578%	173
African / African-American	0.0426%	2,345
Remaining individualsnot grpmax-eligible	0.0288%	3,472
South Asian	0.00439%	22,770
European (non-Finnish)	0.00186%	53,623

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: ITPA
Protein: p.Pro97=
Coding: c.291T>G
MANE Select: NM_033453
dbSNP: rs145329644
Type: single nucleotide variant
Location: chr20:3215308 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.37 · 4 PDB
Residue 97: an α-helix

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

Disease context

inosine triphosphatase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ITPA c.124+1G>A Pathogenic/Likely pathogenic ★★ same condition
ITPA c.124+2T>C Pathogenic ★★ same condition
ITPA c.264-1G>A Pathogenic/Likely pathogenic ★★ same condition
ITPA p.Gln156Ter Pathogenic/Likely pathogenic ★★ same condition
ITPA p.Trp151Ter Pathogenic ★★ same condition
ITPA p.Trp90Ter Pathogenic/Likely pathogenic ★★ same condition
ITPA c.124+5G>A Uncertain significance ★★ same condition
ITPA c.190-3C>A Uncertain significance ★★ same condition

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/itpa-p-pro97 (accessed [today's date]).

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