Is RELA p.Arg329Ter (c.985C>T) pathogenic?

RELA p.Arg329Ter (c.985C>T) is classified Pathogenic/Likely pathogenic in RELA (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-09-25). Ultra-rare (popmax 0.0165%, mid); Associated with autoinflammatory disease, familial, Behcet-like-3.

What condition is associated with RELA p.Arg329Ter (c.985C>T)?

RELA p.Arg329Ter (c.985C>T) is associated with autoinflammatory disease, familial, Behcet-like-3 (ClinVar).

How common is RELA p.Arg329Ter (c.985C>T) in the general population?

RELA p.Arg329Ter (c.985C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

RELA p.Arg329Ter

Q: How is Combined immunodeficiency due to RELA haploinsufficiency inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

c.985C>T · rs1193014025 · VCV1075392

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Conditions

autoinflammatory disease, familial, Behcet-like-3

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (10 of 11, 48 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 1.9, phastCons 1
Overall
CADD	39.0	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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.2e-05% 1/1,614,098 alleles · ultra-rare exomes 1/1,461,860 · genomes 0/152,238 · joint denominator

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.Arg329Ter
Coding: c.985C>T
MANE Select: NM_021975
dbSNP: rs1193014025
Type: single nucleotide variant
Location: chr11:65655736 (GRCh38)
Gene constraint: LOEUF 0.4 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 73.52 · 88 PDB
Residue 329: the 'disordered' region; a UniProt-annotated variant site (found in a patient diagnosed with autoimmune lymphoproliferative syndrome; uncertain significance)

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

Disease context

autoinflammatory disease, familial, Behcet-like-3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Combined immunodeficiency due to RELA haploinsufficiency (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood

Similar variants

RELA p.Arg329Gly Uncertain significance ★ ⚠ same residue
RELA p.Arg198Ter Pathogenic/Likely pathogenic ★★ same condition
RELA p.Gln372Ter Pathogenic/Likely pathogenic ★★ same condition
RELA p.Arg325Gln Uncertain significance ★★ ⚠ same condition
RELA c.8-10C>T Benign/Likely benign ★★ same condition
RELA p.Asp291Asn Benign/Likely benign ★★ same condition
RELA p.Cys206Ter Likely pathogenic ★ same condition
RELA p.Ser169Ter Likely pathogenic ★ 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/rela-p-arg329ter (accessed [today's date]).

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