Is ICOS p.Ile61fs (c.181del) pathogenic?

ICOS p.Ile61fs (c.181del) is classified Pathogenic in ICOS (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). Absent from gnomAD; Associated with immunodeficiency, common variable, 1.

What condition is associated with ICOS p.Ile61fs (c.181del)?

ICOS p.Ile61fs (c.181del) is associated with immunodeficiency, common variable, 1 (ClinVar).

How common is ICOS p.Ile61fs (c.181del) in the general population?

ICOS p.Ile61fs (c.181del) is absent from gnomAD (gnomAD).

ICOS p.Ile61fs

Q: How is Late-onset combined immunodeficiency due to ICOS deficiency inherited?

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

c.181del · rs1690066397 · VCV940397

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

immunodeficiency, common variable, 1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 5
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP -2.7, phastCons 0.39

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: ICOS
Protein: p.Ile61fs
Coding: c.181del
MANE Select: NM_012092
dbSNP: rs1690066397
Type: Deletion
Location: chr2:203955756 (GRCh38)
Gene constraint: LOEUF 1.273 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.24 · 2 PDB
Residue 61: a β-strand; the ig-like v-type domain; a disulfide bond

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

Disease context

immunodeficiency, common variable, 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Late-onset combined immunodeficiency due to ICOS deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

ICOS p.Leu99fs Pathogenic/Likely pathogenic ★★ same condition
ICOS p.Asp46fs Likely pathogenic ★ same condition
ICOS p.Leu96fs Likely pathogenic ★ same condition
ICOS p.Phe119fs Pathogenic ★ same condition
ICOS p.Thr188_Lys191del Uncertain significance ★ same condition
ICOS c.395-17del Likely benign ★ same condition
ICOS c.59-594_501+93del Pathogenic same condition
ICOS c.58+1G>A Likely 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/icos-p-ile61fs (accessed [today's date]).

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