Is RELB p.Arg563Ser (c.1687C>A) pathogenic?

RELB p.Arg563Ser (c.1687C>A) is classified Uncertain significance in RELB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.7378); No allele count reported in gnomAD v4.1 (AN 1,495,418).

How common is RELB p.Arg563Ser (c.1687C>A) in the general population?

RELB p.Arg563Ser (c.1687C>A) is no allele count reported in gnomAD v4.1 (AN 1,495,418) (gnomAD).

What do computational predictors say about RELB p.Arg563Ser (c.1687C>A)?

AlphaMissense predicts likely pathogenic (score 0.7378) — an in-silico prediction, not a clinical call.

RELB p.Arg563Ser

c.1687C>A · VCV3667014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7378 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,495,418)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7378	likely pathogenic
REVEL	0.086	moderately benign-leaning
SaProt	LLR -4.49	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 0.91, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 12 kb · p 4.5e-06 · regional, not allelic
Overall
CADD	24.1	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

No allele count reported in gnomAD v4.1 (AN 1,495,418). 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.Arg563Ser
Coding: c.1687C>A
MANE Select: NM_006509
Type: single nucleotide variant
Location: chr19:45037737 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB
Residue 563: a UniProt-annotated variant site (in imd53)

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

Similar variants

RELB p.Arg563Cys Uncertain significance ★★ ⚠ same residue
RELB p.Arg563= Likely benign ★★ same residue
RELB p.Arg563His Uncertain significance ★ ⚠ same residue
RELB p.Ala541Asp Uncertain significance ★★ ⚠ same type
RELB p.Ala565Val Uncertain significance ★★ ⚠ same type
RELB p.Arg176Gln Uncertain significance ★★ ⚠ same type
RELB p.Arg211Gln Uncertain significance ★★ ⚠ same type
RELB p.Arg213Gln 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-arg563ser (accessed [today's date]).

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