Is IFNAR2 p.Phe10Ile (c.28T>A) pathogenic?

IFNAR2 p.Phe10Ile (c.28T>A) is classified Uncertain significance in IFNAR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-07-01). AlphaMissense: likely benign (0.0448); Ultra-rare (popmax 0.0293%, afr); Associated with Associated with severe COVID-19 disease.

What condition is associated with IFNAR2 p.Phe10Ile (c.28T>A)?

IFNAR2 p.Phe10Ile (c.28T>A) is associated with Associated with severe COVID-19 disease (ClinVar).

How common is IFNAR2 p.Phe10Ile (c.28T>A) in the general population?

IFNAR2 p.Phe10Ile (c.28T>A) is ultra-rare (popmax 0.0293%, afr) (gnomAD).

What do computational predictors say about IFNAR2 p.Phe10Ile (c.28T>A)?

AlphaMissense predicts likely benign (score 0.0448) — an in-silico prediction, not a clinical call.

IFNAR2 p.Phe10Ile

c.28T>A · rs1051393 · VCV2628357

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0448 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0293%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Associated with severe COVID-19 disease

Computational evidence

Protein change
AlphaMissense	0.0448	likely benign
REVEL	0.009	strongly benign-leaning
SaProt	LLR -7.37	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3	GERP -7
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.36 · regional, not allelic
Overall
CADD	0.002	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0293% African / African-American · 22/74,978 alleles

Filtering AF 0.0198% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0167%

Overall 0.00143% 23/1,612,154 alleles · ultra-rare exomes 16/1,460,014 · genomes 7/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0293%	3,408
European (non-Finnish)	8.48e-05%	1,178,969

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.Phe10Ile
Coding: c.28T>A
MANE Select: NM_001289125
dbSNP: rs1051393
Type: single nucleotide variant
Location: chr21:33241950 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 10: a UniProt-annotated variant site (in)

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

Disease context

Associated with severe COVID-19 disease

Similar variants

IFNAR2 p.Phe10Val Benign/Likely benign ★★ same residue
IFNAR2 p.Ser53Pro Conflicting classifications of pathogenicity ★ ⚠ same condition
IFNAR2 c.98-43T>A Uncertain significance same condition
IFNAR2 p.Asp320= Likely benign same condition
IFNAR2 p.Asp78_Leu79insTer Pathogenic/Likely pathogenic ★★ same condition
IFNAR2 p.Glu104fs Pathogenic/Likely pathogenic ★★ same condition
IFNAR2 c.840+1G>T Uncertain significance ★★ same type
IFNAR2 p.Arg397Gly Uncertain significance ★★ ⚠ same type

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-phe10ile (accessed [today's date]).

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