Is RELB p.Pro314Gln (c.941C>A) pathogenic?

RELB p.Pro314Gln (c.941C>A) is classified Uncertain significance in RELB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-08). AlphaMissense: ambiguous (0.4365); Very rare (popmax 0.000511%, nfe).

How common is RELB p.Pro314Gln (c.941C>A) in the general population?

RELB p.Pro314Gln (c.941C>A) is very rare (popmax 0.000511%, nfe) (gnomAD).

What do computational predictors say about RELB p.Pro314Gln (c.941C>A)?

AlphaMissense predicts ambiguous (score 0.4365) — an in-silico prediction, not a clinical call.

RELB p.Pro314Gln

c.941C>A · rs748518205 · VCV2974465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4365 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000511%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4365	ambiguous
REVEL	0.195	benign-leaning
SaProt	LLR -10.84	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.7	GERP -3.3, phastCons 1
Regional constraint	o/e 0.78	unconstrained · MANE · 12 kb · p 4.5e-06 · regional, not allelic
Overall
CADD	23.3	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 0.000511% European (non-Finnish) · 6/1,173,636 alleles

Filtering AF 0.000184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000121%

Overall 0.000375% 6/1,599,242 alleles · very rare exomes 5/1,447,108 · genomes 1/152,134 · 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.Pro314Gln
Coding: c.941C>A
MANE Select: NM_006509
dbSNP: rs748518205
Type: single nucleotide variant
Location: chr19:45028942 (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.Pro314Leu Uncertain significance ★ ⚠ same residue
RELB p.Pro314= Likely benign ★ same residue
RELB p.Pro314fs 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-pro314gln (accessed [today's date]).

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