Is IFNAR2 p.Pro482His (c.1445C>A) pathogenic?

IFNAR2 p.Pro482His (c.1445C>A) is classified Uncertain significance in IFNAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-18). AlphaMissense: likely benign (0.1093); Very rare (popmax 0.000339%, nfe).

How common is IFNAR2 p.Pro482His (c.1445C>A) in the general population?

IFNAR2 p.Pro482His (c.1445C>A) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about IFNAR2 p.Pro482His (c.1445C>A)?

AlphaMissense predicts likely benign (score 0.1093) — an in-silico prediction, not a clinical call.

IFNAR2 p.Pro482His

c.1445C>A · rs757519908 · VCV2087810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1093 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1093	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -6.53	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 0.41	GERP 0.48
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.36 · regional, not allelic
Overall
CADD	14.88	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 0.000339% European (non-Finnish) · 4/1,180,016 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,613,966 alleles · very rare exomes 2/1,461,874 · genomes 2/152,092 · joint denominator

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.Pro482His
Coding: c.1445C>A
MANE Select: NM_001289125
dbSNP: rs757519908
Type: single nucleotide variant
Location: chr21:33263397 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 482: the 'disordered' region

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

Similar variants

IFNAR2 p.Pro482Ser Uncertain significance ★ ⚠ 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
IFNAR2 p.Asp198Gly Uncertain significance ★★ ⚠ same type
IFNAR2 p.Asp437Gly 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-pro482his (accessed [today's date]).

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