Is IFNAR2 p.Ser392Arg (c.1176T>A) pathogenic?

IFNAR2 p.Ser392Arg (c.1176T>A) is classified Conflicting classifications of pathogenicity in IFNAR2 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-12-01). AlphaMissense: likely benign (0.1983); Rare (popmax 0.561%, afr).

How common is IFNAR2 p.Ser392Arg (c.1176T>A) in the general population?

IFNAR2 p.Ser392Arg (c.1176T>A) is rare (popmax 0.561%, afr) (gnomAD).

What do computational predictors say about IFNAR2 p.Ser392Arg (c.1176T>A)?

AlphaMissense predicts likely benign (score 0.1983) — an in-silico prediction, not a clinical call.

IFNAR2 p.Ser392Arg

c.1176T>A · rs144384060 · VCV1553104

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1983 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.561%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1983	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -7.11	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 -1.5	GERP 4.4
Regional constraint	o/e 0.96	unconstrained · MANE · 22 kb · p 0.36 · regional, not allelic
Overall
CADD	6.898	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.561% African / African-American · 421/75,026 alleles

Filtering AF 0.517% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.499%

Overall 0.029% 468/1,614,144 alleles · rare exomes 233/1,461,892 · genomes 235/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.561%	178
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Admixed American	0.0233%	4,287
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,361
European (non-Finnish)	0.0011%	90,770

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.Ser392Arg
Coding: c.1176T>A
MANE Select: NM_001289125
dbSNP: rs144384060
Type: single nucleotide variant
Location: chr21:33263128 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 392: the 'disordered' region

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

Similar variants

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
IFNAR2 p.Glu184Lys 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-ser392arg (accessed [today's date]).

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