Is RAD21 p.Pro245= (c.735C>T) pathogenic?

RAD21 p.Pro245= (c.735C>T) is classified Conflicting classifications of pathogenicity in RAD21 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-02). Very rare (popmax 0.00794%, nfe); Associated with Inborn genetic diseases.

What condition is associated with RAD21 p.Pro245= (c.735C>T)?

RAD21 p.Pro245= (c.735C>T) is associated with Inborn genetic diseases, Cornelia de Lange syndrome 4 (ClinVar).

How common is RAD21 p.Pro245= (c.735C>T) in the general population?

RAD21 p.Pro245= (c.735C>T) is very rare (popmax 0.00794%, nfe) (gnomAD).

RAD21 p.Pro245=

c.735C>T · rs199767556 · VCV211996

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00794%, nfe)

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 -0.82	GERP -5.3
Overall
CADD	6.893	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00794% European (non-Finnish) · 92/1,158,388 alleles

Filtering AF 0.0066% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00611%

Overall 0.0296% 465/1,573,364 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.14%	88
Remaining individualsnot grpmax-eligible	0.0744%	1,345
European (non-Finnish)grpmax	0.00794%	12,591
Admixed American	0.0018%	55,490
African / African-American	0.00137%	73,128

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro245=
Coding: c.735C>T
MANE Select: NM_006265
dbSNP: rs199767556
Type: single nucleotide variant
Location: chr8:116856725 (GRCh38)
Gene constraint: LOEUF 0.341 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 61.49 · 37 PDB
Residue 245: the 'required for interaction with smarca5' region; a UniProt-annotated variant site (in cdls4)

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 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
RAD21 p.Arg322Thr 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-pro245 (accessed [today's date]).

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