Is RELB p.Arg413Trp (c.1237C>T) pathogenic?

RELB p.Arg413Trp (c.1237C>T) is classified Uncertain significance in RELB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-26). AlphaMissense: likely pathogenic (0.5704); Ultra-rare (popmax 0.0112%, nfe).

How common is RELB p.Arg413Trp (c.1237C>T) in the general population?

RELB p.Arg413Trp (c.1237C>T) is ultra-rare (popmax 0.0112%, nfe) (gnomAD).

What do computational predictors say about RELB p.Arg413Trp (c.1237C>T)?

AlphaMissense predicts likely pathogenic (score 0.5704) — an in-silico prediction, not a clinical call.

RELB p.Arg413Trp

c.1237C>T · rs754531882 · VCV1399067

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5704 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.5704	likely pathogenic
REVEL	0.309	indeterminate
SaProt	LLR -8.22	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 12 kb · p 4.5e-06 · regional, not allelic
Overall
CADD	32.0	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

Grpmax group 0.0112% European (non-Finnish) · 132/1,179,868 alleles

Filtering AF 0.00961% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00855% 138/1,613,852 alleles · ultra-rare exomes 134/1,461,666 · genomes 4/152,186 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0112%	8,938
Remaining individualsnot grpmax-eligible	0.0048%	20,820
African / African-American	0.00267%	37,459
Admixed American	0.00167%	59,994

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.Arg413Trp
Coding: c.1237C>T
MANE Select: NM_006509
dbSNP: rs754531882
Type: single nucleotide variant
Location: chr19:45034273 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB
Residue 413: the rhd domain; 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.Arg413Gln 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
RELB p.Arg213Trp Uncertain significance ★★ ⚠ same type
RELB p.Arg219Gln 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-arg413trp (accessed [today's date]).

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