Is RELB p.Ser273Pro (c.817T>C) pathogenic?

RELB p.Ser273Pro (c.817T>C) is classified Uncertain significance in RELB (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-16). AlphaMissense: likely pathogenic (0.9941); Absent from gnomAD v4.1.

How common is RELB p.Ser273Pro (c.817T>C) in the general population?

RELB p.Ser273Pro (c.817T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RELB p.Ser273Pro (c.817T>C)?

AlphaMissense predicts likely pathogenic (score 0.9941) — an in-silico prediction, not a clinical call.

RELB p.Ser273Pro

c.817T>C · rs2513651495 · VCV2126936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9941	likely pathogenic
REVEL	0.193	benign-leaning
SaProt	LLR -15.35	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 1.2, phastCons 1
Regional constraint	o/e 0.20	constrained · MANE · 63 bp · p 5.2e-05 · regional, not allelic
Overall
CADD	23.5	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

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.Ser273Pro
Coding: c.817T>C
MANE Select: NM_006509
dbSNP: rs2513651495
Type: single nucleotide variant
Location: chr19:45025668 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.97 (gnomAD)
Structure: AlphaFold pLDDT 70.42 · 1 PDB
Residue 273: the rhd domain

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

Similar variants

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
RELB p.Arg219Gln Uncertain significance ★★ ⚠ same type
RELB p.Arg241Trp 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-ser273pro (accessed [today's date]).

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