Is RELB p.Asp486= (c.1458C>T) pathogenic?

RELB p.Asp486= (c.1458C>T) is classified Benign/Likely benign in RELB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-01). Low-frequency (popmax 3.43%, afr); Associated with immunodeficiency 53.

What condition is associated with RELB p.Asp486= (c.1458C>T)?

RELB p.Asp486= (c.1458C>T) is associated with immunodeficiency 53 (ClinVar).

How common is RELB p.Asp486= (c.1458C>T) in the general population?

RELB p.Asp486= (c.1458C>T) is low-frequency (popmax 3.43%, afr) (gnomAD).

RELB p.Asp486=

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.1458C>T · rs77076601 · VCV1168461

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.43%, afr)

Conditions

immunodeficiency 53

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 -5.3	GERP -4.3
Overall
CADD	2.085	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.43% African / African-American · 2,577/75,022 alleles

Filtering AF 3.32% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.28%

Overall 0.176% 2,842/1,613,144 alleles · low-frequency exomes 1,424/1,460,876 · genomes 1,418/152,268 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.43%	29
Remaining individualsnot grpmax-eligible	0.213%	470
Admixed American	0.167%	600
Middle Eastern	0.0825%	1,212
South Asian	0.011%	9,107
European (non-Finnish)	0.00144%	69,397

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: RELB
Protein: p.Asp486=
Coding: c.1458C>T
MANE Select: NM_006509
dbSNP: rs77076601
Type: single nucleotide variant
Location: chr19:45037508 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB
Residue 486: a UniProt-annotated variant site (in imd53)

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.Glu319Lys Uncertain significance ★★ ⚠ same condition
RELB p.Val418Ile Uncertain significance ★★ ⚠ same condition
RELB p.Arg307Ter Conflicting classifications of pathogenicity ★ ⚠ 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
RELB p.Ala565Val 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-asp486 (accessed [today's date]).

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