Is IRF7 p.Ser487Arg (c.1461C>A) pathogenic?

IRF7 p.Ser487Arg (c.1461C>A) is classified Uncertain significance in IRF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-22). AlphaMissense: likely pathogenic (0.8592); Absent from gnomAD v4.1; Associated with immunodeficiency 39.

What condition is associated with IRF7 p.Ser487Arg (c.1461C>A)?

IRF7 p.Ser487Arg (c.1461C>A) is associated with immunodeficiency 39 (ClinVar).

How common is IRF7 p.Ser487Arg (c.1461C>A) in the general population?

IRF7 p.Ser487Arg (c.1461C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about IRF7 p.Ser487Arg (c.1461C>A)?

AlphaMissense predicts likely pathogenic (score 0.8592) — an in-silico prediction, not a clinical call.

IRF7 p.Ser487Arg

Q: How is Predisposition to severe viral infection due to IRF7 deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.1461C>A · rs778977149 · VCV2115368

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8592 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

immunodeficiency 39

Computational evidence

Protein change
AlphaMissense	0.8592	likely pathogenic
REVEL	0.595	indeterminate
SaProt	LLR -8.39	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	phastCons 1
Regional constraint	o/e 1.24	unconstrained · MANE · 2,716 bp · p 9.3e-11 · regional, not allelic
Overall
CADD	22.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: IRF7
Protein: p.Ser487Arg
Coding: c.1461C>A
MANE Select: NM_001572
dbSNP: rs778977149
Type: single nucleotide variant
Location: chr11:612696 (GRCh38)
Gene constraint: LOEUF 1.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 1 PDB
Residue 487: a modified residue (phosphoserine); a UniProt-annotated variant site (abolishes ifnb induction upon sendai virus infection); a UniProt-annotated variant site (abolished ifnb induction upon sendai virus infection)

Full IRF7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

immunodeficiency 39 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Predisposition to severe viral infection due to IRF7 deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages

Similar variants

IRF7 c.20+39G>C Uncertain significance ★★ same condition
IRF7 c.21-16G>A Uncertain significance ★★ same condition
IRF7 c.21-19C>T Uncertain significance ★★ same condition
IRF7 c.848-1G>C Uncertain significance ★★ same condition
IRF7 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
IRF7 p.Ala251Pro Uncertain significance ★★ ⚠ same condition
IRF7 p.Ala258Val Uncertain significance ★★ ⚠ same condition
IRF7 p.Ala259Gly Uncertain significance ★★ ⚠ same condition

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/irf7-p-ser487arg (accessed [today's date]).

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