Is XIAP p.Lys299fs (c.894_898del) pathogenic?

XIAP p.Lys299fs (c.894898del) is classified Pathogenic in XIAP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-09-10). Absent from gnomAD; Associated with XIAP-related disorder.

What condition is associated with XIAP p.Lys299fs (c.894_898del)?

XIAP p.Lys299fs (c.894_898del) is associated with XIAP-related disorder, X-linked lymphoproliferative disease due to XIAP deficiency (ClinVar).

How common is XIAP p.Lys299fs (c.894_898del) in the general population?

XIAP p.Lys299fs (c.894_898del) is absent from gnomAD (gnomAD).

XIAP p.Lys299fs

c.894_898del · rs2148092759 · VCV1162913

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

XIAP-related disorder

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 3 of 7
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 1.7, 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.Lys299fs
Coding: c.894_898del
MANE Select: NM_001167
dbSNP: rs2148092759
Type: Microsatellite
Location: chrX:123888629 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 74 PDB
Residue 299: a UniProt-annotated variant site (in xlp2; uncertain significance); a β-strand

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

Disease context

XIAP-related disorder

Also linked: X-linked lymphoproliferative disease due to XIAP deficiency

Similar variants

XIAP p.Lys299= Likely benign ★ same residue
XIAP p.Gly205del Pathogenic/Likely pathogenic ★★ same condition
XIAP p.Thr486fs Uncertain significance ★★ same condition
XIAP c.1056+13_1056+14del Benign/Likely benign ★★ same condition
XIAP p.Glu350del Conflicting classifications of pathogenicity ★ same condition
XIAP c.1056+21_1056+22del Likely benign ★ same condition
XIAP p.Arg222Ter Pathogenic ★★ same condition
XIAP p.Arg381Ter 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-lys299fs (accessed [today's date]).

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