Is IFNAR2 p.Ser53del (c.158_160del) pathogenic?

IFNAR2 p.Ser53del (c.158160del) is classified Likely pathogenic in IFNAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-11). Very rare (popmax 0.00133%, afr); Associated with immunodeficiency 45.

What condition is associated with IFNAR2 p.Ser53del (c.158_160del)?

IFNAR2 p.Ser53del (c.158_160del) is associated with immunodeficiency 45 (ClinVar).

How common is IFNAR2 p.Ser53del (c.158_160del) in the general population?

IFNAR2 p.Ser53del (c.158_160del) is very rare (popmax 0.00133%, afr) (gnomAD).

IFNAR2 p.Ser53del

c.158_160del · rs1468003457 · VCV3068469

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

immunodeficiency 45

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.9	GERP 5, phastCons 1

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,980 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000373% 6/1,610,594 alleles · very rare exomes 6/1,458,238 · genomes 0/152,356 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00312%	32,016
African / African-Americangrpmax	0.00133%	74,980
South Asian	0.0011%	91,010
European (non-Finnish)	0.00017%	588,367

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: IFNAR2
Protein: p.Ser53del
Coding: c.158_160del
MANE Select: NM_001289125
dbSNP: rs1468003457
Type: Deletion
Location: chr21:33245009 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 53: a β-strand

Full IFNAR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 45 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

IFNAR2 p.Ser53Pro Conflicting classifications of pathogenicity ★ ⚠ same residue
IFNAR2 p.Asp78_Leu79insTer Pathogenic/Likely pathogenic ★★ same condition
IFNAR2 p.Glu104fs Pathogenic/Likely pathogenic ★★ same condition
IFNAR2 p.Ile185fs Pathogenic ★★ same condition
IFNAR2 c.840+1G>T Uncertain significance ★★ same condition
IFNAR2 p.Glu356Gly Uncertain significance ★★ ⚠ same condition
IFNAR2 c.541-50A>G Benign ★★ same condition
IFNAR2 p.Phe10Val Benign/Likely benign ★★ 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/ifnar2-p-ser53del (accessed [today's date]).

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