Is RELB p.Val47Ala (c.140T>C) pathogenic?

RELB p.Val47Ala (c.140T>C) is classified Uncertain significance in RELB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-17). AlphaMissense: likely benign (0.0799); Very rare (popmax 0.00186%, nfe).

How common is RELB p.Val47Ala (c.140T>C) in the general population?

RELB p.Val47Ala (c.140T>C) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about RELB p.Val47Ala (c.140T>C)?

AlphaMissense predicts likely benign (score 0.0799) — an in-silico prediction, not a clinical call.

RELB p.Val47Ala

c.140T>C · rs774030958 · VCV2957834

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0799 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0799	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -5.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.48	GERP 0.36, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 24 kb · p 0.018 · regional, not allelic
Overall
CADD	13.86	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 0.00186% European (non-Finnish) · 22/1,179,710 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00149% 24/1,613,246 alleles · very rare exomes 23/1,461,130 · genomes 1/152,116 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00186%	53,623
Remaining individualsnot grpmax-eligible	0.0016%	62,436
African / African-American	0.00133%	74,910

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.Val47Ala
Coding: c.140T>C
MANE Select: NM_006509
dbSNP: rs774030958
Type: single nucleotide variant
Location: chr19:45002982 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB
Residue 47: the 'leucine-zipper' region

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

Similar variants

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RELB p.Arg211Gln Uncertain significance ★★ ⚠ same type
RELB p.Arg213Gln Uncertain significance ★★ ⚠ same type
RELB p.Arg213Trp Uncertain significance ★★ ⚠ same type
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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-val47ala (accessed [today's date]).

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