Is ITPA p.Phe132= (c.396C>T) pathogenic?

ITPA p.Phe132= (c.396C>T) is classified Likely benign in ITPA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-14). Very rare (popmax 0.00223%, eas); Associated with inosine triphosphatase deficiency.

What condition is associated with ITPA p.Phe132= (c.396C>T)?

ITPA p.Phe132= (c.396C>T) is associated with inosine triphosphatase deficiency (ClinVar).

How common is ITPA p.Phe132= (c.396C>T) in the general population?

ITPA p.Phe132= (c.396C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

ITPA p.Phe132=

c.396C>T · rs756108585 · VCV2802405

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

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 1.5, phastCons 1
Overall
CADD	10.6	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,876 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000496% 8/1,613,048 alleles · very rare exomes 8/1,460,694 · genomes 0/152,354 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,876
South Asian	0.0022%	45,534
European (non-Finnish)	0.000424%	235,870

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.Phe132=
Coding: c.396C>T
MANE Select: NM_033453
dbSNP: rs756108585
Type: single nucleotide variant
Location: chr20:3218617 (GRCh38)
Gene constraint: LOEUF 1.159 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.37 · 4 PDB
Residue 132: a β-strand

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.Phe132Leu 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-phe132 (accessed [today's date]).

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