Is IRF8 p.Pro310= (c.930C>T) pathogenic?

IRF8 p.Pro310= (c.930C>T) is classified Likely benign in IRF8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). Very rare (popmax 0.004%, afr); Associated with Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency.

How common is IRF8 p.Pro310= (c.930C>T) in the general population?

IRF8 p.Pro310= (c.930C>T) is very rare (popmax 0.004%, afr) (gnomAD).

IRF8 p.Pro310=

Q: What condition is associated with IRF8 p.Pro310= (c.930C>T)?

IRF8 p.Pro310= (c.930C>T) is associated with Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency, immunodeficiency 32B (ClinVar).

Q: How is Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency inherited?

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

c.930C>T · VCV3748616

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Conditions

Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency

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 1.7	GERP 1.4, phastCons 1
Overall
CADD	12.08	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,952 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,612,368 alleles · very rare exomes 2/1,460,090 · genomes 1/152,278 · 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: IRF8
Protein: p.Pro310=
Coding: c.930C>T
MANE Select: NM_002163
Type: single nucleotide variant
Location: chr16:85918745 (GRCh38)
Gene constraint: LOEUF 0.462 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 75.54

Full IRF8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: immunodeficiency 32B

For Mendelian susceptibility to mycobacterial diseases due to partial IRF8 deficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Infancy, Neonatal

Similar variants

IRF8 p.Arg140His Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg228Cys Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg268Trp Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg296Cys Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg315His Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg340Trp Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg361Gly Uncertain significance ★★ ⚠ same condition
IRF8 p.Arg375Trp 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/irf8-p-pro310 (accessed [today's date]).

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