Is CTLA4 p.Val73fs (c.216dup) pathogenic?

CTLA4 p.Val73fs (c.216dup) is classified Pathogenic in CTLA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-12). Absent from gnomAD; Associated with autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency.

What condition is associated with CTLA4 p.Val73fs (c.216dup)?

CTLA4 p.Val73fs (c.216dup) is associated with autoimmune lymphoproliferative syndrome due to CTLA4 haploinsufficiency (ClinVar).

How common is CTLA4 p.Val73fs (c.216dup) in the general population?

CTLA4 p.Val73fs (c.216dup) is absent from gnomAD (gnomAD).

CTLA4 p.Val73fs

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.216dup · rs2469719282 · VCV2097298

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 2 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5	GERP 1.4, 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: CTLA4
Protein: p.Val73fs
Coding: c.216dup
MANE Select: NM_005214
dbSNP: rs2469719282
Type: Duplication
Location: chr2:203870691 (GRCh38)
Gene constraint: LOEUF 0.211 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.67 · 22 PDB
Residue 73: a disulfide bond; a β-strand; the ig-like v-type domain

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.Val73= Likely benign ★ same residue
CTLA4 p.Gly142_Ile143insMetGly Likely pathogenic ★ same condition
CTLA4 p.Met91fs Pathogenic ★ same condition
CTLA4 p.Tyr177fs Conflicting classifications of pathogenicity ★ ⚠ same condition
CTLA4 p.Ala121fs Pathogenic ★★★ same condition
CTLA4 p.Arg51Ter Pathogenic ★★★ same condition
CTLA4 p.Arg75Trp Pathogenic ★★★ ⚠ same condition
CTLA4 p.Asp153Asn 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-val73fs (accessed [today's date]).

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