Is XIAP p.Ser40= (c.120T>C) pathogenic?

XIAP p.Ser40= (c.120T>C) is classified Likely benign in XIAP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). Absent from gnomAD v4.1; Associated with X-linked lymphoproliferative disease due to XIAP deficiency.

What condition is associated with XIAP p.Ser40= (c.120T>C)?

XIAP p.Ser40= (c.120T>C) is associated with X-linked lymphoproliferative disease due to XIAP deficiency (ClinVar).

How common is XIAP p.Ser40= (c.120T>C) in the general population?

XIAP p.Ser40= (c.120T>C) is absent from gnomAD v4.1 (gnomAD).

XIAP p.Ser40=

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.120T>C · VCV4745587

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>G here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.5	GERP -3.5, phastCons 1
Overall
CADD	8.064	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: XIAP
Protein: p.Ser40=
Coding: c.120T>C
MANE Select: NM_001167
Type: single nucleotide variant
Location: chrX:123885782 (GRCh38)
Structure: AlphaFold pLDDT 74.60 · 74 PDB
Residue 40: a β-strand

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.Arg222Ter Pathogenic ★★ same condition
XIAP p.Arg381Ter Pathogenic ★★ same condition
XIAP p.Glu337Ter Pathogenic ★★ same condition
XIAP p.His220Tyr Likely pathogenic ★★ same condition
XIAP p.Tyr115Ter Pathogenic ★★ same condition
XIAP p.Ala137Gly Uncertain significance ★★ ⚠ same condition
XIAP p.Ala68Val Uncertain significance ★★ ⚠ same condition
XIAP p.Ala79Thr 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/xiap-p-ser40 (accessed [today's date]).

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