Is IFNAR2 p.Pro362Ala (c.1084C>G) pathogenic?

IFNAR2 p.Pro362Ala (c.1084C>G) is classified Uncertain significance in IFNAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-10-20). AlphaMissense: likely benign (0.0654); Very rare (popmax 0.00167%, amr).

How common is IFNAR2 p.Pro362Ala (c.1084C>G) in the general population?

IFNAR2 p.Pro362Ala (c.1084C>G) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about IFNAR2 p.Pro362Ala (c.1084C>G)?

AlphaMissense predicts likely benign (score 0.0654) — an in-silico prediction, not a clinical call.

IFNAR2 p.Pro362Ala

c.1084C>G · rs1441207963 · VCV1063769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0654 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0654	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -6.08	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 -0.79	GERP 0.59
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.36 · regional, not allelic
Overall
CADD	2.633	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 0.00167% Admixed American · 1/60,008 alleles

Overall 6.84e-05% 1/1,461,890 alleles · very rare

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.Pro362Ala
Coding: c.1084C>G
MANE Select: NM_001289125
dbSNP: rs1441207963
Type: single nucleotide variant
Location: chr21:33263036 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 362: a UniProt-annotated variant site (no effect on activation of stat1 upon ifna2 or ifng binding); the 'disordered' region

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

Similar variants

IFNAR2 p.Pro362Leu Uncertain significance ★★ ⚠ same residue
IFNAR2 p.Pro362Ser Uncertain significance ★ ⚠ same residue
IFNAR2 p.Pro362= Benign ★ same residue
IFNAR2 c.840+1G>T Uncertain significance ★★ same type
IFNAR2 p.Arg397Gly Uncertain significance ★★ ⚠ same type
IFNAR2 p.Arg90Gly Uncertain significance ★★ ⚠ same type
IFNAR2 p.Asn146Ser Uncertain significance ★★ ⚠ same type
IFNAR2 p.Asn281Tyr 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-pro362ala (accessed [today's date]).

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