Is XIAP p.Pro37fs (c.108del) pathogenic?

XIAP p.Pro37fs (c.108del) is classified Pathogenic in XIAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-02-08). No gnomAD frequency available for this variant; Associated with X-linked lymphoproliferative disease due to XIAP deficiency.

What condition is associated with XIAP p.Pro37fs (c.108del)?

XIAP p.Pro37fs (c.108del) is associated with X-linked lymphoproliferative disease due to XIAP deficiency (ClinVar).

How common is XIAP p.Pro37fs (c.108del) in the general population?

XIAP p.Pro37fs (c.108del) is no gnomAD frequency available for this variant (gnomAD).

XIAP p.Pro37fs

Q: How is X-linked lymphoproliferative disease due to XIAP deficiency inherited?

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

c.108del · rs1556404455 · VCV503904

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

X-linked lymphoproliferative disease due to XIAP deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7	GERP 0.64, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: XIAP
Protein: p.Pro37fs
Coding: c.108del
MANE Select: NM_001167
dbSNP: rs1556404455
Type: Deletion
Location: chrX:123885767 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 74 PDB

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

Disease context

X-linked lymphoproliferative disease due to XIAP deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For X-linked lymphoproliferative disease due to XIAP deficiency (Orphanet):

Inheritance: X-linked recessive
Onset: Adolescent, Adult, Childhood, Infancy

Similar variants

XIAP p.Asn341fs Pathogenic ★★ same condition
XIAP p.Asp130fs Pathogenic ★★ same condition
XIAP p.Tyr329fs Pathogenic ★★ same condition
XIAP c.1057-600_1300+79del Pathogenic ★ same condition
XIAP c.-32-5232_878-647del Likely pathogenic ★ same condition
XIAP p.Arg124fs Pathogenic ★ same condition
XIAP p.Glu21fs Pathogenic ★ same condition
XIAP p.Leu141fs Pathogenic ★ 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/xiap-p-pro37fs (accessed [today's date]).

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