Is RAD21 p.Asp262= (c.786C>T) pathogenic?

RAD21 p.Asp262= (c.786C>T) is classified Benign/Likely benign in RAD21 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Rare (popmax 0.914%, afr); Associated with Inborn genetic diseases.

What condition is associated with RAD21 p.Asp262= (c.786C>T)?

RAD21 p.Asp262= (c.786C>T) is associated with Inborn genetic diseases, Cornelia de Lange syndrome 4 (ClinVar).

How common is RAD21 p.Asp262= (c.786C>T) in the general population?

RAD21 p.Asp262= (c.786C>T) is rare (popmax 0.914%, afr) (gnomAD).

RAD21 p.Asp262=

c.786C>T · rs34653007 · VCV473194

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.914%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -4, phastCons 0.46
Overall
CADD	8.52	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.914% African / African-American · 676/73,970 alleles

Filtering AF 0.857% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.834%

Overall 0.0462% 737/1,594,966 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.914%	109
Remaining individualsnot grpmax-eligible	0.0519%	1,925
Admixed American	0.0261%	3,835
South Asian	0.00567%	17,634
European (non-Finnish)	0.000769%	130,059

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: RAD21
Protein: p.Asp262=
Coding: c.786C>T
MANE Select: NM_006265
dbSNP: rs34653007
Type: single nucleotide variant
Location: chr8:116856674 (GRCh38)
Gene constraint: LOEUF 0.341 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.49 · 37 PDB
Residue 262: the 'required for interaction with smarca5' region; a UniProt-annotated variant site (in cdls4); the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Cornelia de Lange syndrome 4

Similar variants

RAD21 p.Asp262Val Uncertain significance ★ ⚠ same residue
RAD21 c.144+1G>A Pathogenic ★★ same condition
RAD21 p.Arg478Ter Pathogenic/Likely pathogenic ★★ same condition
RAD21 p.Arg54Trp Likely pathogenic ★★ same condition
RAD21 p.Arg65Ter Pathogenic/Likely pathogenic ★★ same condition
RAD21 p.Gln436Ter Pathogenic/Likely pathogenic ★★ same condition
RAD21 p.Gly408Ter Pathogenic ★★ same condition
RAD21 p.Ala410Thr Uncertain significance ★★ ⚠ same condition

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-asp262 (accessed [today's date]).

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