Is ITPA p.Pro143= (c.429C>A) pathogenic?

ITPA p.Pro143= (c.429C>A) is classified Likely benign in ITPA (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-19). Absent from gnomAD v4.1; Associated with inosine triphosphatase deficiency.

What condition is associated with ITPA p.Pro143= (c.429C>A)?

ITPA p.Pro143= (c.429C>A) is associated with inosine triphosphatase deficiency (ClinVar).

How common is ITPA p.Pro143= (c.429C>A) in the general population?

ITPA p.Pro143= (c.429C>A) is absent from gnomAD v4.1 (gnomAD).

ITPA p.Pro143=

c.429C>A · rs2067472388 · VCV2098761

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 -0.83	GERP -5.1, phastCons 0.003
Overall
CADD	3.439	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ITPA
Protein: p.Pro143=
Coding: c.429C>A
MANE Select: NM_033453
dbSNP: rs2067472388
Type: single nucleotide variant
Location: chr20:3221858 (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 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-pro143 (accessed [today's date]).

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