Is RELB p.Asp487Asn (c.1459G>A) pathogenic?

RELB p.Asp487Asn (c.1459G>A) is classified Uncertain significance in RELB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-23). AlphaMissense: likely benign (0.112); Ultra-rare (popmax 0.033%, mid).

How common is RELB p.Asp487Asn (c.1459G>A) in the general population?

RELB p.Asp487Asn (c.1459G>A) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about RELB p.Asp487Asn (c.1459G>A)?

AlphaMissense predicts likely benign (score 0.112) — an in-silico prediction, not a clinical call.

RELB p.Asp487Asn

c.1459G>A · rs144038804 · VCV1959524

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.112 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.112	likely benign
REVEL	0.052	moderately benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.7	GERP 1, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 12 kb · p 4.5e-06 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000372% 6/1,613,088 alleles · ultra-rare exomes 2/1,460,828 · genomes 4/152,260 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
African / African-American	0.00267%	37,516
Admixed American	0.00167%	59,978
European (non-Finnish)	8.48e-05%	1,179,729

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.Asp487Asn
Coding: c.1459G>A
MANE Select: NM_006509
dbSNP: rs144038804
Type: single nucleotide variant
Location: chr19:45037509 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB
Residue 487: 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.Asp487Tyr Uncertain significance ★★ ⚠ same residue
RELB p.Asp487= Likely benign ★ 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

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-asp487asn (accessed [today's date]).

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