Is ITPA p.Phe31= (c.93T>C) pathogenic?

ITPA p.Phe31= (c.93T>C) is classified Likely benign in ITPA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-07). Very rare (popmax 0.00533%, afr); Associated with inosine triphosphatase deficiency.

What condition is associated with ITPA p.Phe31= (c.93T>C)?

ITPA p.Phe31= (c.93T>C) is associated with inosine triphosphatase deficiency (ClinVar).

How common is ITPA p.Phe31= (c.93T>C) in the general population?

ITPA p.Phe31= (c.93T>C) is very rare (popmax 0.00533%, afr) (gnomAD).

ITPA p.Phe31=

c.93T>C · rs555480105 · VCV794439

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00533%, 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 1.1	GERP 2.4, phastCons 1
Overall
CADD	9.975	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,066 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000434% 7/1,614,222 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00533%	18,767
Admixed American	0.00167%	60,022
Remaining individualsnot grpmax-eligible	0.0016%	62,512
European (non-Finnish)	8.47e-05%	1,180,013

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.Phe31=
Coding: c.93T>C
MANE Select: NM_033453
dbSNP: rs555480105
Type: single nucleotide variant
Location: chr20:3213195 (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.Phe31fs Pathogenic ★ 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-phe31 (accessed [today's date]).

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