Is RELB p.Pro314fs (c.939del) pathogenic?

RELB p.Pro314fs (c.939del) is classified Uncertain significance in RELB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-06). Very rare (popmax 0.00017%, nfe).

How common is RELB p.Pro314fs (c.939del) in the general population?

RELB p.Pro314fs (c.939del) is very rare (popmax 0.00017%, nfe) (gnomAD).

RELB p.Pro314fs

c.939del · rs1568403698 · VCV2797227

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 8 of 12
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -9.7	GERP -4.3

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,174,052 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000125% 2/1,600,322 alleles · very rare exomes 2/1,448,074 · genomes 0/152,248 · joint denominator

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.Pro314fs
Coding: c.939del
MANE Select: NM_006509
dbSNP: rs1568403698
Type: Deletion
Location: chr19:45028938 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB
Residue 314: the rhd domain

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

Similar variants

RELB p.Pro314Gln Uncertain significance ★ ⚠ same residue
RELB p.Pro314Leu Uncertain significance ★ ⚠ same residue
RELB p.Pro314= Likely benign ★ same residue
RELB p.Asp39fs Uncertain significance ★ same type
RELB p.Pro75_Glu77delinsGln Uncertain significance ★ same type
RELB c.106+16del Benign ★ same type
RELB c.107-9_107-7del Likely benign ★ same type
RELB c.1208-18del Likely benign ★ 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-pro314fs (accessed [today's date]).

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