Is ZAP70 p.Pro91= (c.273C>T) pathogenic?

ZAP70 p.Pro91= (c.273C>T) is classified Likely benign in ZAP70 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). No allele count reported in gnomAD v4.1 (AN 1,588,298); Associated with combined immunodeficiency due to ZAP70 deficiency.

What condition is associated with ZAP70 p.Pro91= (c.273C>T)?

ZAP70 p.Pro91= (c.273C>T) is associated with combined immunodeficiency due to ZAP70 deficiency (ClinVar).

How common is ZAP70 p.Pro91= (c.273C>T) in the general population?

ZAP70 p.Pro91= (c.273C>T) is no allele count reported in gnomAD v4.1 (AN 1,588,298) (gnomAD).

ZAP70 p.Pro91=

Q: How is Combined immunodeficiency due to ZAP70 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.273C>T · VCV3625702

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,588,298)

Conditions

combined immunodeficiency due to ZAP70 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 -3.1	GERP -3.3
Overall
CADD	10.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,588,298). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ZAP70
Protein: p.Pro91=
Coding: c.273C>T
MANE Select: NM_001079
Type: single nucleotide variant
Location: chr2:97724309 (GRCh38)
Gene constraint: LOEUF 0.624 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.91 · 15 PDB
Residue 91: the sh2 1 domain

Full ZAP70 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

combined immunodeficiency due to ZAP70 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to ZAP70 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood

Similar variants

ZAP70 c.1624-11G>A Pathogenic ★★ same condition
ZAP70 p.Arg37Gly Pathogenic/Likely pathogenic ★★ same condition
ZAP70 p.Arg465Cys Likely pathogenic ★★ same condition
ZAP70 c.1083-3C>A Uncertain significance ★★ same condition
ZAP70 c.403-3T>C Uncertain significance ★★ same condition
ZAP70 c.790+6G>A Uncertain significance ★★ same condition
ZAP70 c.837+6T>C Uncertain significance ★★ same condition
ZAP70 c.889+6C>T 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/zap70-p-pro91 (accessed [today's date]).

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