Is RELB p.Arg307Ter (c.919C>T) pathogenic?

RELB p.Arg307Ter (c.919C>T) is classified Conflicting classifications of pathogenicity in RELB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-08-18). No allele count reported in gnomAD v4.1 (AN 1,600,434); Associated with immunodeficiency 53.

What condition is associated with RELB p.Arg307Ter (c.919C>T)?

RELB p.Arg307Ter (c.919C>T) is associated with immunodeficiency 53 (ClinVar).

How common is RELB p.Arg307Ter (c.919C>T) in the general population?

RELB p.Arg307Ter (c.919C>T) is no allele count reported in gnomAD v4.1 (AN 1,600,434) (gnomAD).

RELB p.Arg307Ter

Q: How is Combined immunodeficiency due to RELB deficiency inherited?

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

c.919C>T · rs1971589003 · VCV973569

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,600,434)

Conditions

immunodeficiency 53

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 8 of 12
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.15	GERP -1.8, phastCons 0.96
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,600,434). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: RELB
Protein: p.Arg307Ter
Coding: c.919C>T
MANE Select: NM_006509
dbSNP: rs1971589003
Type: single nucleotide variant
Location: chr19:45028920 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB
Residue 307: the rhd domain

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

Disease context

immunodeficiency 53 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to RELB deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

RELB p.Arg307Gln Uncertain significance ★ ⚠ same residue
RELB p.Glu319Lys Uncertain significance ★★ ⚠ same condition
RELB p.Val418Ile Uncertain significance ★★ ⚠ same condition
RELB p.Asp486= Benign/Likely benign ★★ same condition
RELB p.Leu571Phe Uncertain significance ★ ⚠ same condition
RELB p.Tyr397Ter Pathogenic same condition
RELB p.Gln135dup Uncertain significance same condition
RELB p.Ala541Asp 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/relb-p-arg307ter (accessed [today's date]).

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