Is IFNAR2 p.Ser412= (c.1236C>T) pathogenic?

IFNAR2 p.Ser412= (c.1236C>T) is classified Likely benign in IFNAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-19). Very rare (popmax 0.00223%, eas).

How common is IFNAR2 p.Ser412= (c.1236C>T) in the general population?

IFNAR2 p.Ser412= (c.1236C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

IFNAR2 p.Ser412=

c.1236C>T · rs748444111 · VCV2801506

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.15	GERP 3.6
Overall
CADD	2.955	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,882 alleles

Overall 0.000186% 3/1,614,202 alleles · very rare exomes 3/1,461,886 · genomes 0/152,316 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,882
Admixed American	0.00167%	60,022
European (non-Finnish)	8.47e-05%	1,180,032

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.Ser412=
Coding: c.1236C>T
MANE Select: NM_001289125
dbSNP: rs748444111
Type: single nucleotide variant
Location: chr21:33263188 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 412: the 'disordered' region

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

Similar variants

IFNAR2 p.Ser412Arg Uncertain significance ★ ⚠ same residue
IFNAR2 p.Ser412Gly 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

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-ser412 (accessed [today's date]).

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