Is RELB p.Pro121Ala (c.361C>G) pathogenic?

RELB p.Pro121Ala (c.361C>G) is classified Uncertain significance in RELB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-15). AlphaMissense: likely benign (0.0532); Absent from gnomAD v4.1.

How common is RELB p.Pro121Ala (c.361C>G) in the general population?

RELB p.Pro121Ala (c.361C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RELB p.Pro121Ala (c.361C>G)?

AlphaMissense predicts likely benign (score 0.0532) — an in-silico prediction, not a clinical call.

RELB p.Pro121Ala

c.361C>G · rs2513638370 · VCV2800673

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0532 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0532	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.12	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 0.14	GERP 0.43, phastCons 0.22
Regional constraint	o/e 0.88	unconstrained · MANE · 24 kb · p 0.018 · regional, not allelic
Overall
CADD	8.378	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RELB
Protein: p.Pro121Ala
Coding: c.361C>G
MANE Select: NM_006509
dbSNP: rs2513638370
Type: single nucleotide variant
Location: chr19:45012133 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB

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

Similar variants

RELB p.Pro121Gln Uncertain significance ★ ⚠ same residue
RELB p.Pro121Leu Uncertain significance ★ ⚠ same residue
RELB p.Pro121= 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

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-pro121ala (accessed [today's date]).

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