Is IRF7 p.Ser73Arg (c.219C>G) pathogenic?

IRF7 p.Ser73Arg (c.219C>G) is classified Uncertain significance in IRF7 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-12-18). AlphaMissense: likely benign (0.2336); Very rare (popmax 0.00359%, sas); Associated with immunodeficiency 39.

What condition is associated with IRF7 p.Ser73Arg (c.219C>G)?

IRF7 p.Ser73Arg (c.219C>G) is associated with immunodeficiency 39 (ClinVar).

How common is IRF7 p.Ser73Arg (c.219C>G) in the general population?

IRF7 p.Ser73Arg (c.219C>G) is very rare (popmax 0.00359%, sas) (gnomAD).

What do computational predictors say about IRF7 p.Ser73Arg (c.219C>G)?

AlphaMissense predicts likely benign (score 0.2336) — an in-silico prediction, not a clinical call.

IRF7 p.Ser73Arg

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.219C>G · rs926854541 · VCV1494732

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2336 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00359%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

immunodeficiency 39

Computational evidence

Protein change
AlphaMissense	0.2336	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -4.76	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 0.83
Regional constraint	o/e 1.24	unconstrained · MANE · 2,716 bp · p 9.3e-11 · regional, not allelic
Overall
CADD	13.52	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 0.00359% South Asian · 3/83,526 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000465%

Overall 0.000193% 3/1,553,454 alleles · very rare exomes 3/1,401,088 · genomes 0/152,366 · 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: IRF7
Protein: p.Ser73Arg
Coding: c.219C>G
MANE Select: NM_001572
dbSNP: rs926854541
Type: single nucleotide variant
Location: chr11:614972 (GRCh38)
Gene constraint: LOEUF 1.766 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 1 PDB
Residue 73: a DNA-binding region; the 'disordered' region

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 p.Ser73Asn Uncertain significance ★ ⚠ same residue
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

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-ser73arg (accessed [today's date]).

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