Is IFNAR2 p.Asp437= (c.1311C>T) pathogenic?

IFNAR2 p.Asp437= (c.1311C>T) is classified Likely benign in IFNAR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). Very rare (popmax 0.00668%, eas).

How common is IFNAR2 p.Asp437= (c.1311C>T) in the general population?

IFNAR2 p.Asp437= (c.1311C>T) is very rare (popmax 0.00668%, eas) (gnomAD).

IFNAR2 p.Asp437=

c.1311C>T · VCV4739702

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, 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 -9.5	GERP -3.6
Overall
CADD	0.905	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% East Asian · 3/44,894 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.00143% 23/1,614,040 alleles · very rare exomes 22/1,461,892 · genomes 1/152,148 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00668%	14,965
Admixed American	0.00667%	15,001
African / African-American	0.00267%	37,449
South Asian	0.0022%	45,545
Remaining individualsnot grpmax-eligible	0.0016%	62,490
European (non-Finnish)	0.000932%	107,276

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.Asp437=
Coding: c.1311C>T
MANE Select: NM_001289125
Type: single nucleotide variant
Location: chr21:33263263 (GRCh38)
Gene constraint: LOEUF 0.761 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.86 · 9 PDB
Residue 437: the 'mediates interaction with stat2 (and required for the recruitment of usp18)' region

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

Similar variants

IFNAR2 p.Asp437Gly Uncertain significance ★★ ⚠ same residue
IFNAR2 p.Asp437del 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-asp437 (accessed [today's date]).

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