Is CTLA4 p.Pro32fs (c.94_101delinsTTCTCTTCATCA) pathogenic?

CTLA4 p.Pro32fs (c.94101delinsTTCTCTTCATCA) is classified Pathogenic in CTLA4 (ClinVar, Expert panel, 1 submitter; last evaluated 2025-11-24). Associated with autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency.

What condition is associated with CTLA4 p.Pro32fs (c.94_101delinsTTCTCTTCATCA)?

CTLA4 p.Pro32fs (c.94_101delinsTTCTCTTCATCA) is associated with autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency (ClinVar).

CTLA4 p.Pro32fs

Q: How is Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency inherited?

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

c.94_101delinsTTCTCTTCATCA · VCV4683125

Pathogenic Expert panel

Classification

Pathogenic

ClinVar

Review

Expert panel ★★★☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency

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 LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 2.1, phastCons 1

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

Variant & gene context

Gene: CTLA4
Protein: p.Pro32fs
Coding: c.94_101delinsTTCTCTTCATCA
MANE Select: NM_005214
Type: Indel
Location: chr2:203868036 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.67 · 22 PDB

Full CTLA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Autoimmune lymphoproliferative syndrome due to CTLA4 haploinsuffiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult, Childhood

Similar variants

CTLA4 p.Pro32Ala Uncertain significance ★ ⚠ same residue
CTLA4 p.Pro32Ser Uncertain significance ★ ⚠ same residue
CTLA4 p.Gln42Ter Pathogenic ★ same condition
CTLA4 p.His39fs Pathogenic ★ same condition
CTLA4 p.Gly146Leu Uncertain significance ★ same condition
CTLA4 p.Ala121fs Pathogenic ★★★ same condition
CTLA4 p.Arg51Ter Pathogenic ★★★ same condition
CTLA4 p.Arg75Trp 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/ctla4-p-pro32fs (accessed [today's date]).

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