Is RELA p.Arg236Ter (c.706C>T) pathogenic?

RELA p.Arg236Ter (c.706C>T) is classified Pathogenic/Likely pathogenic in RELA (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-09). Very rare (popmax 0.00017%, nfe); Associated with RELA-related disorder.

What condition is associated with RELA p.Arg236Ter (c.706C>T)?

RELA p.Arg236Ter (c.706C>T) is associated with RELA-related disorder (ClinVar).

How common is RELA p.Arg236Ter (c.706C>T) in the general population?

RELA p.Arg236Ter (c.706C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

RELA p.Arg236Ter

c.706C>T · rs1856484601 · VCV851182

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Conditions

RELA-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 8 of 11
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.5	GERP -5.4, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,178,920 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,612,582 alleles · very rare exomes 3/1,460,318 · genomes 0/152,264 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,448
European (non-Finnish)grpmax	0.00017%	589,459

Remaining individuals 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: RELA
Protein: p.Arg236Ter
Coding: c.706C>T
MANE Select: NM_021975
dbSNP: rs1856484601
Type: single nucleotide variant
Location: chr11:65658458 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.52 · 88 PDB
Residue 236: the rhd domain; a β-strand

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

Disease context

RELA-related disorder

Similar variants

RELA p.Arg236Gln Uncertain significance ★★ ⚠ same residue
RELA c.1034-2A>C Likely pathogenic ★ same condition
RELA p.Gln442Ter Conflicting classifications of pathogenicity ★ ⚠ same condition
RELA p.Gln508His Likely benign same condition
RELA p.Ala345fs Likely pathogenic ★ same condition
RELA p.His88fs Likely pathogenic same condition
RELA p.Arg198Ter Pathogenic/Likely pathogenic ★★ same type
RELA p.Arg329Ter Pathogenic/Likely pathogenic ★★ 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/rela-p-arg236ter (accessed [today's date]).

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