Is ITPA p.Arg144= (c.432A>G) pathogenic?

ITPA p.Arg144= (c.432A>G) is classified Likely benign in ITPA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-30). Very rare (popmax 0.00134%, afr); Associated with inosine triphosphatase deficiency.

What condition is associated with ITPA p.Arg144= (c.432A>G)?

ITPA p.Arg144= (c.432A>G) is associated with inosine triphosphatase deficiency (ClinVar).

How common is ITPA p.Arg144= (c.432A>G) in the general population?

ITPA p.Arg144= (c.432A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

ITPA p.Arg144=

c.432A>G · rs1197304382 · VCV2730870

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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 2.1	GERP -1.6, phastCons 1
Overall
CADD	9.782	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,904 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000248% 4/1,613,866 alleles · very rare exomes 2/1,461,716 · genomes 2/152,150 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,904
European (non-Finnish)	0.000254%	393,335

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.Arg144=
Coding: c.432A>G
MANE Select: NM_033453
dbSNP: rs1197304382
Type: single nucleotide variant
Location: chr20:3221861 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.37 · 4 PDB

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 p.Arg144Lys Uncertain significance ★ ⚠ same residue
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

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-arg144 (accessed [today's date]).

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