Is RAD21 p.Pro286Arg (c.857C>G) pathogenic?

RAD21 p.Pro286Arg (c.857C>G) is classified Uncertain significance in RAD21 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-25). AlphaMissense: likely benign (0.2178); Absent from gnomAD v4.1.

How common is RAD21 p.Pro286Arg (c.857C>G) in the general population?

RAD21 p.Pro286Arg (c.857C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about RAD21 p.Pro286Arg (c.857C>G)?

AlphaMissense predicts likely benign (score 0.2178) — an in-silico prediction, not a clinical call.

RAD21 p.Pro286Arg

c.857C>G · VCV3370167

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2178 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2178	likely benign
REVEL	0.247	benign-leaning
SaProt	LLR -8.07	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 12	GERP 2.7, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 5,665 bp · p 2e-05 · regional, not allelic
Overall
CADD	28.5	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: RAD21
Protein: p.Pro286Arg
Coding: c.857C>G
MANE Select: NM_006265
Type: single nucleotide variant
Location: chr8:116856246 (GRCh38)
Gene constraint: LOEUF 0.341 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.49 · 37 PDB
Residue 286: a UniProt-annotated variant site (in cdls4)

Full RAD21 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RAD21 c.144+1G>A Pathogenic ★★ same type
RAD21 p.Arg478Ter Pathogenic/Likely pathogenic ★★ same type
RAD21 p.Arg54Trp Likely pathogenic ★★ same type
RAD21 p.Arg65Ter Pathogenic/Likely pathogenic ★★ same type
RAD21 p.Gln436Ter Pathogenic/Likely pathogenic ★★ same type
RAD21 p.Gly408Ter Pathogenic ★★ same type
RAD21 p.Tyr3Ter Likely pathogenic ★★ same type
RAD21 p.Ala410Thr 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/rad21-p-pro286arg (accessed [today's date]).

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